One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between...One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.展开更多
Leopoldamys edwardsi is a species with wide distribution ranges in southern China but is not discussed in studies on geographic variation and species differentiation.We used 2 mitochondrial(Cytb,CO1)and 3 nuclea...Leopoldamys edwardsi is a species with wide distribution ranges in southern China but is not discussed in studies on geographic variation and species differentiation.We used 2 mitochondrial(Cytb,CO1)and 3 nuclear(GHR,IRBP and RAG1)genes to clarify species phylogeography and geographical differentiation.Maximum likelihood(ML)and Bayesian phylogenetic inference(BI)trees consistently indicated that L.edwardsi is a species complex containing 3 main lineages with high Kimura-2-parameter(K2P)divergences(i.e.lineages LN,LS and LHN)found in the northern and southern China and Hainan Island,respectively.The 3 species delimitation methods,automated barcoding gap discovery,Bayesian poisson tree process analysis and Bayesian phylogenetics and phylogeography,consistently supported the existence of cryptic species.Divergence times among the main lineages were inferred to be during the Pleistocene,with LHN/LS split at 1.33 Ma and LN/(LHN+LS)at 2.61 Ma;the diversifications of L.edwardsi complex might be caused by the rapid uplifts of Tibetan Plateau,paleoclimate change and complex topography.The divergence between LHN and LS was probably related to the separation of Hainan Island from the mainland via the formation of the Qiongzhou Strait.Lineages LN and(LS+LHN)likely diverged due to the Wuyi-Nanling mountain range forming a dispersal barrier.Our results suggested that L.edwardsi complex contains at least 3 distinct species:LHN represents L.hainanensis,endemic to Hainan Island and previously considered as a subspecies L.e.hainanensis;LS represents a cryptic species distributed throughout the southern Chinese continent;and LN represents the nominotypical species L.edwardsi.展开更多
基金supported by the National Natural Science Foundation of China(82070593)the Zhejiang Provincial Natural Science Foundation(LD21H030002)+1 种基金the Department of Science and Technology of Zhejiang Province(ZY2019008)the Youth Program of the National Natural Science Foundation of China(82200632).
文摘One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.
基金the Major International(Regional)Joint Research Project of NSFC(Grant No.31110103910)the Japan Society for the Promotion of Science(JSPS)Core-to-Core Program B Asia-Africa Scientific Platforms,and the JSPS Grants-in-Aid for Scientific Research(26304009).
文摘Leopoldamys edwardsi is a species with wide distribution ranges in southern China but is not discussed in studies on geographic variation and species differentiation.We used 2 mitochondrial(Cytb,CO1)and 3 nuclear(GHR,IRBP and RAG1)genes to clarify species phylogeography and geographical differentiation.Maximum likelihood(ML)and Bayesian phylogenetic inference(BI)trees consistently indicated that L.edwardsi is a species complex containing 3 main lineages with high Kimura-2-parameter(K2P)divergences(i.e.lineages LN,LS and LHN)found in the northern and southern China and Hainan Island,respectively.The 3 species delimitation methods,automated barcoding gap discovery,Bayesian poisson tree process analysis and Bayesian phylogenetics and phylogeography,consistently supported the existence of cryptic species.Divergence times among the main lineages were inferred to be during the Pleistocene,with LHN/LS split at 1.33 Ma and LN/(LHN+LS)at 2.61 Ma;the diversifications of L.edwardsi complex might be caused by the rapid uplifts of Tibetan Plateau,paleoclimate change and complex topography.The divergence between LHN and LS was probably related to the separation of Hainan Island from the mainland via the formation of the Qiongzhou Strait.Lineages LN and(LS+LHN)likely diverged due to the Wuyi-Nanling mountain range forming a dispersal barrier.Our results suggested that L.edwardsi complex contains at least 3 distinct species:LHN represents L.hainanensis,endemic to Hainan Island and previously considered as a subspecies L.e.hainanensis;LS represents a cryptic species distributed throughout the southern Chinese continent;and LN represents the nominotypical species L.edwardsi.
