AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response media...AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.展开更多
After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been full...After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.展开更多
Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17...Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.展开更多
AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus ...AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age- and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20?°C. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson’s correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS: The mean vitamin D level in HCV patients (group?I) was 15 ± 5.2 ng/mL while in control (group II) was 39.7 ± 10.8. For active vitamin D in group?I?as 16.6 ± 4.8 ng/mL while in group II was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group?I?and 6.7 ± 2.17 in group II. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group?I?and 216.1 ± 5.38 in group II. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and -23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group?Ia with bright hepatomegaly and included 14 patients. Group?Ib with perihepatic fibrosis and included 11 patients. Group?Ic with liver cirrhosis and included 11 patients. Group?Id with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). CONCLUSION: Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.展开更多
Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to dete...Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.展开更多
The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the...The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the context of cancer are also shaped by CD4 T cells, which can directly affect cancer prognosis in patients. While the proinflammatory mediator interleukin(IL)-1β was initially shown to enhance Th2 cell responses, recent findings support a predominant role of two other members of the IL-1 family, IL-18 and IL-33, on the production of Th1 and Th2-derived cytokines. In addition, IL-1β was found to profoundly affect the biology of two recently identified CD4 T cell subsets, Th17 and Th9 cells. IL-1β is critical for Th17 cell differentiation and it enhances the production of IL-9 and IL-21 by Th9 cells, thus increasing their anticancer properties. We will here review the mechanisms accounting for the ability of IL-1 cytokines to affect the differentiation of CD4 effector T cells with a focus on Th17 and Th9 cells. The physiopathological relevance of IL-1-driven effects on CD4 T cells will also be discussed.展开更多
The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mati...The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mation. IBD including Crohn＇s disease （CD） and ulcerative colitis （UC） is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Thl- mediated inflammatory disorder while UC is regarded as a Th2-1ike disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Thl or Th2 cells, and several cytokines [e.g. interleukin （IL）-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Thl/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.展开更多
The dendritic cell vaccine is a treatment vaccine with potent clinical applications.Functional cytokines can enhance dendritic cell anti-tumor immune responses.This experiment was conducted to study the effects of bon...The dendritic cell vaccine is a treatment vaccine with potent clinical applications.Functional cytokines can enhance dendritic cell anti-tumor immune responses.This experiment was conducted to study the effects of bone marrow-derived dendritic cells(BM-DCs)modified with genes encoding murine interleukin-23(IL-23)on murine pancreatic carcinoma,and effects of the treatment of pancreatic carcinoma with β-elemene combined with IL-23-modified dendritic cell vaccine.The murine IL-23 cDNA was sub-cloned into a dual-expression vector.DCs were pulsed with tumor cell lysate after being modified wth IL-23.Mice were divided into groups which were injected with IL-23-transduced DC vaccine,non-transduced DC vaccine and sodium respectively.The preventive immune and immunotherapeutic effects of DC vaccines on mice and cytokine release in vivo were then assessed.Results showed inhibitory effects on tumor cells and increased survival time in the experimental group treated with the vaccine combined with β-elemene.The IL-23 protein apparently increases the antigen presenting ability of DCs.After injection with DC vaccines,IFN-γ production in the treatment group was significantly increased as compared with that in the control group(P<0.01),and IL-4 production was decreased as compared with that in the control group(P<0.05).Tumor size was obviously reduced,and survival time clearly prolonged in the group with β-elemene combined with DC vaccine,in comparison to the other treatment groups and the control(P<0.01).IL-23-modified dendritic cell vaccines enhance specific Th1-type and cytotoxic T lymphocyte(CTL)responses against pancreatic carcinoma cells,and induce not only auto-immune ability but also preventive immunity against pancreatic carcinoma implanted in mice.β-elemene has great anti-tumor collaborative functions.展开更多
Reactive arthritis （ReA）, also known as sterile postin-fectious arthritis, belongs to the group of related ar-thropathies known as spondyloarthritis （SpA）. ReA can arise 1-4 wk after a gastrointestinal or genitour...Reactive arthritis （ReA）, also known as sterile postin-fectious arthritis, belongs to the group of related ar-thropathies known as spondyloarthritis （SpA）. ReA can arise 1-4 wk after a gastrointestinal or genitourinary infection, but once arthritis develops, the microorgan-ism is not found in the joint. The classical microbes as-sociated with ReA development include Gram-negative aerobic or microaerophilic bacteria containing LPS in their outer membrane. The immunopathogenic mechanisms involved in ReA development are still unknown. A hypothesis suggested that the bacteria probably persist outside the joint, at sites such as gut mucosa or lymph nodes, and bacterial antigens might then be transported to the joints. On the other hand, an altered immune response and the unbalanced production of cy-tokines have been reported in subjects with ReA. Currently, there is increased evidence to suggest that both mechanisms would operate in the immunopathogenesis of ReA. In this review we highlight recent advances on the role of cytokines in the ReA. Particularly, we discuss the roles of some pro- and anti-infammatory cytokines involved in the immunopathogenesis of ReA.展开更多
Interleukin-17(IL-17)and IL-17-producing cells have been shown to play important roles in inflammation and the immune response.IL-17 is believed to be mainly produced by T helper 17(Th17)cells,a unique helper T-cell s...Interleukin-17(IL-17)and IL-17-producing cells have been shown to play important roles in inflammation and the immune response.IL-17 is believed to be mainly produced by T helper 17(Th17)cells,a unique helper T-cell subset different from Th1 and Th2 cells.Other subsets of T cells such as cdT and natural killer T(NKT)cells have also been found to produce IL-17 in response to innate stimuli.IL-17 acts as a proinflammatory cytokine that can induce the release of certain chemokines,cytokines,matrix metalloproteinases(MMPs)and antimicrobial peptides from mesenchymal and myeloid cells.This leads to the expansion and accumulation of neutrophils in the innate immune system and links innate and adaptive immunity in vivo.Furthermore,increasing evidence indicates that IL-17 and IL-17-producing cells are involved in the pathogenesis of various diseases such as allergies,autoimmune diseases,allograft transplantation and even malignancy.They may also play protective roles in host defense against infectious diseases and promote induction of cytotoxic T lymphocyte(CTL)responses against cancer.Targeting of the IL-17 axis is under investigation for the treatment of inflammatory disorders.展开更多
Background Interleukin-23 （IL-23） is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration ...Background Interleukin-23 （IL-23） is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration of IL-23 is elevated in patients with rheumatoid arthritis （RA）, and to determine the relationship between the IL-23 level and disease activity in RA patients. Methods Serum samples were obtained from 59 patients with RA and 30 healthy controls. The clinical parameters of disease activity were determined, including the 28-joint disease activity score （DAS28）, C-reactive protein （CRP）, rheumatoid factor （RF） levels, and the degree of bony erosions based on X-rays. The levels of IL-23 and IL-17 were determined by enzyme-linked immunosorbent assay （ELISA）. The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Results The serum IL-23 level was significantly elevated in patients with RA compared to healthy controls. The serum IL-23 levels in the RA patients correlated with IL-17 and CRP levels, and the DAS28. The levels of IL-23 based on X-ray classification phase I, II, III, and IV were gradually elevated in RA patients. Conclusions The levels of serum IL-23 in RA patients were higher than in healthy controls. Thus, elevated serum IL-23 levels may be useful markers to detect active RA. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA.展开更多
BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC r...BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC remains under debate.AIM To clarify the role ofγδT17 cells in patients with mild-to-moderate UC.METHODS A single-centre observational pragmatic study was conducted on patients with UC who attended the outpatient and inpatient departments of Xiyuan Hospital of the China Academy of Traditional Chinese Medicine from September 2020 to December 2022.The research population consisted of two groups of adult patients.The first group consisted of healthy volunteers with no significant abnormalities on colonoscopy,and the other group consisted of patients with mild-to-moderate ulcerative colitis.Serum samples from healthy volunteers and patients with UC were collected for the detection of relevant inflammatory factors.Moreover,five colon mucosa samples were randomly selected from each group for testing and analyses.RESULTS An increased number ofγδT17 cells and hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway were observed in colonic mucosal tissues from patients with UC.CONCLUSION Hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway promotes the activation ofγδT17 cells in colonic mucosal tissues of patients with UC.展开更多
Objective： To observe the regulatory effects of herbal cake-partitioned moxibustion on Crohn＇s disease （CD） rat＇s colon inflammatory cytokine interleukin-17 （IL-17）, IL-23 and their mRNAs, and to investigate th...Objective： To observe the regulatory effects of herbal cake-partitioned moxibustion on Crohn＇s disease （CD） rat＇s colon inflammatory cytokine interleukin-17 （IL-17）, IL-23 and their mRNAs, and to investigate the action mechanism of moxibustion in treating CD. Methods： Forty SPF grade Sprague-Dauley （SD） male rats were randomly divided into a normal group, a model group, an herbal cake-partitioned moxibustion group and a Western medicine group, with 20 rats in each group. Except the normal group, rats in the other three groups were used to make CD model by giving an enema in colon with Trinitro-benzene-sulfonic acid （TNBS）. When the models were successful made, rats in the model group had no therapeutic intervention; rats in the herbal cake-partitioned moxibustion group were subjected to herbal cake-partitioned moxibustion treatment at bilateral Tianshu （ST 25） plus O.ihai （CV 6）; and rats in the Western medicine group were given oral Mesalazine. After treatment, the histopathological changes and inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were observed in descending colon by hematoxylin-eosin （HE） staining, immunohistochemistry （IHC） and real-time polymerase chain reaction （RT-PCR） methods. Results： Colon tissues of TNBS enema rat models showed cracks-like ulcers accompanied by mucous layer inflammation, granulomas, and inflammatory cytokines IL-27, IL-23 and their mRNAs expressions were all higher than those in the normal group （P〈O.01）; after intervention, colon tissue cracks-like ulcers and inflammation degree reduced, inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were all significantly decreased （P〈0.01） in the herbal cake-partitioned moxibustion group and the Western medicine group. Conclusion： Herbal cake-partitioned moxibustion may improve colon tissue ulcers and relieve intestinal inflammation by down-regulation of IL-17, IL-23 and their mRNAs expressions in CD model rats＇ colonic mucosa.展开更多
OBJECTIVE:To investigate the mechanism by which Daifan San(DFS)prevents and treats primary biliary cirrhosis(PBC)via the forkhead box P3(FoxP3)and interleukin(IL)-23/IL-17A signaling pathways.METHODS:Ninety C57BL/6 mi...OBJECTIVE:To investigate the mechanism by which Daifan San(DFS)prevents and treats primary biliary cirrhosis(PBC)via the forkhead box P3(FoxP3)and interleukin(IL)-23/IL-17A signaling pathways.METHODS:Ninety C57BL/6 mice were randomly divided into the control,model,DFS low-dose,DFS middle-dose,DFS high-dose and ursodeoxycholic acid(UDCA)groups(n=15 per group).A mouse model of PBC was induced using polyinosinic polycytidylic acids(poly I:C).Lymphocyte subset expression in the peripheral blood was analyzed via flow cytometry.The inflammatory cytokines and antimitochondrial autoantibody(AMA)levels were detected via enzyme-linked immunosorbent assays.The expressions and location of typeⅠcollagen,typeⅢcollagen,cytokeratin 19 and FoxP3 in the liver tissue were evaluated via immunohistochemistry.FoxP3,IL-23 and IL-17 expressions in the peripheral blood and liver tissue were evaluated via real-time polymerase chain reaction and western blotting.RESULTS:IL-17,IL-23,IL-8,IL-33,TNF-α,and AMA expressions were significantly increased in the model group and decreased in the DFS and UDCA groups.Conversely,Treg cell and FoxP3 expressions were significantly decreased in the model group and increased in the DFS and UDCA groups.The IL-23/IL-17A signaling pathway was closely correlated with chronic inflammation of the bile duct in PBC and functional deletion of Treg cells,leading to reduced FoxP3 levels and mediating the loss of tolerance in PBC.CONCLUSION:DFS may delay the occurrence and relieve the symptoms of PBC by downregulating IL-23/IL-17A signaling pathway expression and upregulating FoxP3 expression.展开更多
Systemic lupus erythematosus（SLE） is a typical autoimmune disease. Lymphotoxin β receptor（LTβR） signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has b...Systemic lupus erythematosus（SLE） is a typical autoimmune disease. Lymphotoxin β receptor（LTβR） signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has been used to treat SLE, while its mechanism remains to be fully elucidated. In this study, to investigate the expression of LTβR in the T cells of SLE patients and its roles in the pathogenesis of SLE, we isolated the peripheral blood T cells of SLE patients and normal controls to detect expression of LTβR by flow cytometry and RNA assay. T cells were also stimulated with LIGHT, a ligand of LTβR, and then detected for their LTβR expressions and apoptosis by flow cytometry. Also, their expressions of inflammatory factors and receptors were determined by RNA assay. The results showed that LTβR positive cells were 22.75%±6.98% in CD3~＋ cells of SLE patients, while there were almost no LTβR positive cells in CD3~＋ cells of normal persons. Moreover, LTβR expression was remarkably higher in CD3,CD4 and CD8 positive T cells of active SLE patients than non/low active patients（all P〈0.05）, and positively correlated with increased Ig level, decreased complement level and renal damage. Moreover, the stimulation of SLE T cells with LIGHT promoted higher expression of LTβR, IL-23 R and IL-17 A, and apoptosis of T cells. In conclusion,we demonstrated a high expression of LTβR in the T cells of SLE patients which may be associated with pathogenesis of SLE.展开更多
文摘AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.
基金supported by the National Natural Science Foundation of China,No. 81771327 (to BYL)Construction of Central Nervous System Injury Basic Science and Clinical Translational Research PlatformBudget of Beijing Municipal Health Commission 2020, No. PXM2020_026280_000002 (BYL)。
文摘After brain injury, infiltration and abnormal activation of neutrophils damages brain tissue and worsens inflammation, but the mediators that connect activated neutrophils with neuroinflammation have not yet been fully clarified. To identify regulators of neutrophil-mediated neuroinflammation after traumatic brain injury, a mouse model of traumatic brain injury was established by controlled cortical impact. At 7 days post-injury(sub-acute phase), genome-wide transcriptomic data showed that interleukin 17 A-associated signaling pathways were markedly upregulated, suggesting that interleukin 17 A may be involved in neuroinflammation. Double immunofluorescence staining showed that interleukin 17 A was largely secreted by neutrophils rather than by glial cells and neurons. Furthermore, nuclear factor-kappaB and Stat3, both of which are important effectors in interleukin 17 A-mediated proinflammatory responses, were significantly activated. Collectively, our findings suggest that neutrophil-derived interleukin 17 A participates in neutrophil-mediated neuroinflammation during the subacute phase of traumatic brain injury. Therefore, interleukin 17 A may be a promising therapeutic target for traumatic brain injury.
文摘Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades.Cancer has a close relationship with the immune system and,although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity,studies have emphasized their roles in cancer pathogenesis.The Th17 immune response profile is involved in several types of cancer including urogenital,respiratory,gastrointestinal,and skin cancers.This type of immune response exerts pro and antitumor functions through several mechanisms,depending on the context of each tumor,including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment.Among other factors,the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential,which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells.Interleukin(IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment,which allow Th17 cells to prevail in tumors.Moreover,the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers,being associated with variable clinical outcomes.The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.
文摘AIM: To assess vitamin D in hepatitis C patients and its relationship to interleukin (IL)-23, IL-17, and macrophage chemoattractant protein-1 (MCP-1). METHODS: The study was conducted on 50 Egyptian hepatitis C virus (HCV) genotype number IV-infected patients and 25 age- and gender-matched healthy subjects. Venous blood samples were obtained. Samples were allowed to clot and sera were separated by centrifugation and stored at -20?°C. A 25 hydroxy vitamin D assay was carried out using solid phase RIA. A 1,25 dihydroxy vitamin D assay was carried out using a commercial kit purchased from Incstar Corporation. IL-17 and -23 and MCP-1 were assayed by an enzyme immunoassay. Quantitative and qualitative polymerase chain reaction for HCV virus were done by TaqMan technology. Only HCV genotype IV-infected subjects were included in the study. The mean ± SD were determined, a t-test for comparison of means of different parameters was used. Correlation analysis was done using Pearson’s correlation. Differences among different groups were determined using the Kruskal-Wallis test. RESULTS: The mean vitamin D level in HCV patients (group?I) was 15 ± 5.2 ng/mL while in control (group II) was 39.7 ± 10.8. For active vitamin D in group?I?as 16.6 ± 4.8 ng/mL while in group II was 41.9 ± 7.9. IL-23 was 154 ± 97.8 in group?I?and 6.7 ± 2.17 in group II. IL-17 was 70.7 ± 72.5 in cases and 1.2 ± 0.4 in control. MCP-1 was 1582 ± 794.4 in group?I?and 216.1 ± 5.38 in group II. Vitamin D deficiency affected 72% of HCV-infected patients and 0% of the control group. Vitamin D insufficiency existed in 28% of HCV-infected patients and 12% of the control group. One hundred percent of the cirrhotic patients and 40% of non cirrhotic HCV-infected patients had vitamin D deficiency. IL-23, IL-17, and MCP-1 were markedly increased in HCV-infected patients in comparison to controls.A significant negative correlation between vitamin D and IL-17 and -23 and MCP-1 was detected. HCV-infected males and females showed no differences with respect to viral load, vitamin D levels, IL-17, IL-23 and MCP-1. The viral load was negatively correlated with vitamin D and active vitamin D (P = 0.0001 and P = 0.001, respectively), while positively correlated with IL-23, IL-17, and MCP-1. We classified the patients according to sonar findings into four groups. Group?Ia with bright hepatomegaly and included 14 patients. Group?Ib with perihepatic fibrosis and included 11 patients. Group?Ic with liver cirrhosis and included 11 patients. Group?Id with hepatocellular carcinoma (HCC) and included 14 patients. Vitamin D and active vitamin D were shown to be lower in cirrhotic patients and much lower in patients with HCC, and this difference was highly significant (P = 0.0001). IL-17 and -23 and MCP-1 were higher in advanced liver disease) and the differences were highly significant (P = 0.0001). CONCLUSION: Whether the deficiency of vitamin D is related to HCV-induced chronic liver disease or predisposing factor for higher viral load is a matter of debate.
文摘Hepatitis B virus reactivation(HBVr)can occur in patients treated with immunosuppressive medications.Risk stratification for HBVr based on hepatitis B virus(HBV)serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use.Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies.Tumor necrosis factor(TNF)-αinhibitors have been widely used for patients with inflammatory bowel disease,psoriasis,and rheumatic diseases.Further,the clinical benefits of interleukin(IL)-12/23,IL-17,or Janus kinases inhibitors have been demonstrated in these patients.It is well known that TNF-αinhibitor use can lead to HBVr,however,the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood.In this review,we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics,and immunological mechanisms of these medications causing HBVr.
基金Supported by Fondation de France (to Apetoh L and Rivera Vargas T)the Association pour la recherche sur le cancer (to Apetoh L)+6 种基金the Institut Mérieux (to Apetoh L)the Conseil Régional de Bourgogne (to Apetoh L)the FEDER,the Agence Nationale de la Recherche,No.ANR-13-JSV3-0001 (to Apetoh L) and No.ANR-11-LABX-0021the ARSEP (to Apetoh L)the Ligue Régionale contre le cancer Comité Grand-Est (to Apetoh L)the European Commission (Marie Curie Fellowship PCIG10-GA-2011-303719)the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No.677251)
文摘The ability of CD4 T cells to differentiate into various effector or regulatory T cell subsets explains the successful adaptation of immune responses to different types of infectious pathogens. Immune responses in the context of cancer are also shaped by CD4 T cells, which can directly affect cancer prognosis in patients. While the proinflammatory mediator interleukin(IL)-1β was initially shown to enhance Th2 cell responses, recent findings support a predominant role of two other members of the IL-1 family, IL-18 and IL-33, on the production of Th1 and Th2-derived cytokines. In addition, IL-1β was found to profoundly affect the biology of two recently identified CD4 T cell subsets, Th17 and Th9 cells. IL-1β is critical for Th17 cell differentiation and it enhances the production of IL-9 and IL-21 by Th9 cells, thus increasing their anticancer properties. We will here review the mechanisms accounting for the ability of IL-1 cytokines to affect the differentiation of CD4 effector T cells with a focus on Th17 and Th9 cells. The physiopathological relevance of IL-1-driven effects on CD4 T cells will also be discussed.
基金Supported by Grants From the National Natural Science Foundation of China,No.30770988 and No.30971358
文摘The etiopathology of inflammatory bowel disease （IBD） remains elusive. Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in intestinal inflam- mation. IBD including Crohn＇s disease （CD） and ulcerative colitis （UC） is a chronic inflammatory disease of the gastrointestinal tract, which is implicated in an inappropriate and overactive mucosal immune response to luminal flora. Traditionally, CD is regarded as a Thl- mediated inflammatory disorder while UC is regarded as a Th2-1ike disease. Recently, Th17 cells were identified as a new subset of T helper cells unrelated to Thl or Th2 cells, and several cytokines [e.g. interleukin （IL）-21, IL-23] are involved in regulating their activation and differentiation. They not only play an important role in host defense against extracellular pathogens, but are also associated with the development of autoimmunity and inflammatory response such as IBD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Thl/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of IBD.
文摘The dendritic cell vaccine is a treatment vaccine with potent clinical applications.Functional cytokines can enhance dendritic cell anti-tumor immune responses.This experiment was conducted to study the effects of bone marrow-derived dendritic cells(BM-DCs)modified with genes encoding murine interleukin-23(IL-23)on murine pancreatic carcinoma,and effects of the treatment of pancreatic carcinoma with β-elemene combined with IL-23-modified dendritic cell vaccine.The murine IL-23 cDNA was sub-cloned into a dual-expression vector.DCs were pulsed with tumor cell lysate after being modified wth IL-23.Mice were divided into groups which were injected with IL-23-transduced DC vaccine,non-transduced DC vaccine and sodium respectively.The preventive immune and immunotherapeutic effects of DC vaccines on mice and cytokine release in vivo were then assessed.Results showed inhibitory effects on tumor cells and increased survival time in the experimental group treated with the vaccine combined with β-elemene.The IL-23 protein apparently increases the antigen presenting ability of DCs.After injection with DC vaccines,IFN-γ production in the treatment group was significantly increased as compared with that in the control group(P<0.01),and IL-4 production was decreased as compared with that in the control group(P<0.05).Tumor size was obviously reduced,and survival time clearly prolonged in the group with β-elemene combined with DC vaccine,in comparison to the other treatment groups and the control(P<0.01).IL-23-modified dendritic cell vaccines enhance specific Th1-type and cytotoxic T lymphocyte(CTL)responses against pancreatic carcinoma cells,and induce not only auto-immune ability but also preventive immunity against pancreatic carcinoma implanted in mice.β-elemene has great anti-tumor collaborative functions.
基金Supported by Agencia Nacional de Promoción Científica y Tecnológica,No.PICT 2008-763,PICT 2011-732by the National University of San Luis(Project 0401)+1 种基金by the Scientific Career of National Council of Scientific and Technical Investigationsby National Council of Scientific and Technical Investigations
文摘Reactive arthritis （ReA）, also known as sterile postin-fectious arthritis, belongs to the group of related ar-thropathies known as spondyloarthritis （SpA）. ReA can arise 1-4 wk after a gastrointestinal or genitourinary infection, but once arthritis develops, the microorgan-ism is not found in the joint. The classical microbes as-sociated with ReA development include Gram-negative aerobic or microaerophilic bacteria containing LPS in their outer membrane. The immunopathogenic mechanisms involved in ReA development are still unknown. A hypothesis suggested that the bacteria probably persist outside the joint, at sites such as gut mucosa or lymph nodes, and bacterial antigens might then be transported to the joints. On the other hand, an altered immune response and the unbalanced production of cy-tokines have been reported in subjects with ReA. Currently, there is increased evidence to suggest that both mechanisms would operate in the immunopathogenesis of ReA. In this review we highlight recent advances on the role of cytokines in the ReA. Particularly, we discuss the roles of some pro- and anti-infammatory cytokines involved in the immunopathogenesis of ReA.
文摘Interleukin-17(IL-17)and IL-17-producing cells have been shown to play important roles in inflammation and the immune response.IL-17 is believed to be mainly produced by T helper 17(Th17)cells,a unique helper T-cell subset different from Th1 and Th2 cells.Other subsets of T cells such as cdT and natural killer T(NKT)cells have also been found to produce IL-17 in response to innate stimuli.IL-17 acts as a proinflammatory cytokine that can induce the release of certain chemokines,cytokines,matrix metalloproteinases(MMPs)and antimicrobial peptides from mesenchymal and myeloid cells.This leads to the expansion and accumulation of neutrophils in the innate immune system and links innate and adaptive immunity in vivo.Furthermore,increasing evidence indicates that IL-17 and IL-17-producing cells are involved in the pathogenesis of various diseases such as allergies,autoimmune diseases,allograft transplantation and even malignancy.They may also play protective roles in host defense against infectious diseases and promote induction of cytotoxic T lymphocyte(CTL)responses against cancer.Targeting of the IL-17 axis is under investigation for the treatment of inflammatory disorders.
基金This research was supported by a grant from the National Natural Science Foundation of China （No. 81072450）
文摘Background Interleukin-23 （IL-23） is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration of IL-23 is elevated in patients with rheumatoid arthritis （RA）, and to determine the relationship between the IL-23 level and disease activity in RA patients. Methods Serum samples were obtained from 59 patients with RA and 30 healthy controls. The clinical parameters of disease activity were determined, including the 28-joint disease activity score （DAS28）, C-reactive protein （CRP）, rheumatoid factor （RF） levels, and the degree of bony erosions based on X-rays. The levels of IL-23 and IL-17 were determined by enzyme-linked immunosorbent assay （ELISA）. The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Results The serum IL-23 level was significantly elevated in patients with RA compared to healthy controls. The serum IL-23 levels in the RA patients correlated with IL-17 and CRP levels, and the DAS28. The levels of IL-23 based on X-ray classification phase I, II, III, and IV were gradually elevated in RA patients. Conclusions The levels of serum IL-23 in RA patients were higher than in healthy controls. Thus, elevated serum IL-23 levels may be useful markers to detect active RA. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA.
基金Supported by China Academy of Chinese Medical Sciences Outstanding Young Talents(Innovative)Cultivation Project,No.ZZ17-YQ-007Special Project of the National Natural Science Foundation of China,No.82341233.
文摘BACKGROUND The interleukin-17(IL-17)mediated aberrant immune-inflammatory response plays a paramount role in ulcerative colitis(UC).γδT17 cells are one of the critical sources of IL-17,but the role they play in UC remains under debate.AIM To clarify the role ofγδT17 cells in patients with mild-to-moderate UC.METHODS A single-centre observational pragmatic study was conducted on patients with UC who attended the outpatient and inpatient departments of Xiyuan Hospital of the China Academy of Traditional Chinese Medicine from September 2020 to December 2022.The research population consisted of two groups of adult patients.The first group consisted of healthy volunteers with no significant abnormalities on colonoscopy,and the other group consisted of patients with mild-to-moderate ulcerative colitis.Serum samples from healthy volunteers and patients with UC were collected for the detection of relevant inflammatory factors.Moreover,five colon mucosa samples were randomly selected from each group for testing and analyses.RESULTS An increased number ofγδT17 cells and hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway were observed in colonic mucosal tissues from patients with UC.CONCLUSION Hyperactivation of the NLR family pyrin domain containing 3/IL-1βsignaling pathway promotes the activation ofγδT17 cells in colonic mucosal tissues of patients with UC.
基金supported by National Basic Research Program of China(973 Program,No.2015CB554501)Natural Science Foundation of Shanghai(No.13ZR1439400)+1 种基金Program for New Century Excellent Talents in University(No.NCET-13-0907)Leading Academic Discipline Project of Shanghai(No.JZ2012019)~~
文摘Objective： To observe the regulatory effects of herbal cake-partitioned moxibustion on Crohn＇s disease （CD） rat＇s colon inflammatory cytokine interleukin-17 （IL-17）, IL-23 and their mRNAs, and to investigate the action mechanism of moxibustion in treating CD. Methods： Forty SPF grade Sprague-Dauley （SD） male rats were randomly divided into a normal group, a model group, an herbal cake-partitioned moxibustion group and a Western medicine group, with 20 rats in each group. Except the normal group, rats in the other three groups were used to make CD model by giving an enema in colon with Trinitro-benzene-sulfonic acid （TNBS）. When the models were successful made, rats in the model group had no therapeutic intervention; rats in the herbal cake-partitioned moxibustion group were subjected to herbal cake-partitioned moxibustion treatment at bilateral Tianshu （ST 25） plus O.ihai （CV 6）; and rats in the Western medicine group were given oral Mesalazine. After treatment, the histopathological changes and inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were observed in descending colon by hematoxylin-eosin （HE） staining, immunohistochemistry （IHC） and real-time polymerase chain reaction （RT-PCR） methods. Results： Colon tissues of TNBS enema rat models showed cracks-like ulcers accompanied by mucous layer inflammation, granulomas, and inflammatory cytokines IL-27, IL-23 and their mRNAs expressions were all higher than those in the normal group （P〈O.01）; after intervention, colon tissue cracks-like ulcers and inflammation degree reduced, inflammatory cytokines IL-17, IL-23 and their mRNAs expressions were all significantly decreased （P〈0.01） in the herbal cake-partitioned moxibustion group and the Western medicine group. Conclusion： Herbal cake-partitioned moxibustion may improve colon tissue ulcers and relieve intestinal inflammation by down-regulation of IL-17, IL-23 and their mRNAs expressions in CD model rats＇ colonic mucosa.
基金The Science and Technology Bureau of Wuhan,China(No.2015061701011646)the Key Projects of the Hubei Provincial Education Department(No.D20112001)。
文摘OBJECTIVE:To investigate the mechanism by which Daifan San(DFS)prevents and treats primary biliary cirrhosis(PBC)via the forkhead box P3(FoxP3)and interleukin(IL)-23/IL-17A signaling pathways.METHODS:Ninety C57BL/6 mice were randomly divided into the control,model,DFS low-dose,DFS middle-dose,DFS high-dose and ursodeoxycholic acid(UDCA)groups(n=15 per group).A mouse model of PBC was induced using polyinosinic polycytidylic acids(poly I:C).Lymphocyte subset expression in the peripheral blood was analyzed via flow cytometry.The inflammatory cytokines and antimitochondrial autoantibody(AMA)levels were detected via enzyme-linked immunosorbent assays.The expressions and location of typeⅠcollagen,typeⅢcollagen,cytokeratin 19 and FoxP3 in the liver tissue were evaluated via immunohistochemistry.FoxP3,IL-23 and IL-17 expressions in the peripheral blood and liver tissue were evaluated via real-time polymerase chain reaction and western blotting.RESULTS:IL-17,IL-23,IL-8,IL-33,TNF-α,and AMA expressions were significantly increased in the model group and decreased in the DFS and UDCA groups.Conversely,Treg cell and FoxP3 expressions were significantly decreased in the model group and increased in the DFS and UDCA groups.The IL-23/IL-17A signaling pathway was closely correlated with chronic inflammation of the bile duct in PBC and functional deletion of Treg cells,leading to reduced FoxP3 levels and mediating the loss of tolerance in PBC.CONCLUSION:DFS may delay the occurrence and relieve the symptoms of PBC by downregulating IL-23/IL-17A signaling pathway expression and upregulating FoxP3 expression.
文摘Systemic lupus erythematosus（SLE） is a typical autoimmune disease. Lymphotoxin β receptor（LTβR） signaling plays an important role in autoimmune inflammations. LTβR-Ig fusion protein, LTβR blocking agent, has been used to treat SLE, while its mechanism remains to be fully elucidated. In this study, to investigate the expression of LTβR in the T cells of SLE patients and its roles in the pathogenesis of SLE, we isolated the peripheral blood T cells of SLE patients and normal controls to detect expression of LTβR by flow cytometry and RNA assay. T cells were also stimulated with LIGHT, a ligand of LTβR, and then detected for their LTβR expressions and apoptosis by flow cytometry. Also, their expressions of inflammatory factors and receptors were determined by RNA assay. The results showed that LTβR positive cells were 22.75%±6.98% in CD3~＋ cells of SLE patients, while there were almost no LTβR positive cells in CD3~＋ cells of normal persons. Moreover, LTβR expression was remarkably higher in CD3,CD4 and CD8 positive T cells of active SLE patients than non/low active patients（all P〈0.05）, and positively correlated with increased Ig level, decreased complement level and renal damage. Moreover, the stimulation of SLE T cells with LIGHT promoted higher expression of LTβR, IL-23 R and IL-17 A, and apoptosis of T cells. In conclusion,we demonstrated a high expression of LTβR in the T cells of SLE patients which may be associated with pathogenesis of SLE.
