Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity.Genetics and environmental factors may contribute to the development of these autoimmune dis...Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity.Genetics and environmental factors may contribute to the development of these autoimmune disorders.Although the etiology and pathogenesis of these disorders are poorly understood,environmental variables that induce aberrant epigenetic regulations may provide some insights.Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences.The most important epigenetic mechanisms are DNA methylation,histone modification,and noncoding RNAs.In this review,we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders,including systemic lupus erythematosus,bullous skin diseases,psoriasis,and systemic sclerosis.These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.展开更多
Outer membrane vesicles(OMVs)are spherical particles shed from the outer membrane of Gram-negative bacteria,which contain the typical components present in the outer membrane,although enrichment of specific molecules ...Outer membrane vesicles(OMVs)are spherical particles shed from the outer membrane of Gram-negative bacteria,which contain the typical components present in the outer membrane,although enrichment of specific molecules may occur,and furthermore a variety of periplasmic components and occasionally some inner membrane or cytoplasmic fractions.Although the detailed mechanisms of OMV biogenesis are not fully illuminated yet,several models have been proposed that demonstrate OMV biogenesis is an orchestrated well-regulated process.OMV secretion offers a way for both intra-and inter-species bacterial communication and for interaction or modulation of the bacterial environment.Therefore,OMVs have proven to be functionally versatile and important for bacterial physiology and survival of the host environment.In the host,OMVs are internalized via host cell endocytosis pathways,allowing them to subsequently trigger a variety of cellular responses.In this review,we discuss the recent advances in establishing the mechanisms involved in OMV biogenesis and the impact of OMVs on bacterial physiology and intracellular modulation of the host.展开更多
Current therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness.To address this limitation,our focus was on CD132,a subunit common to six inflammatory fact...Current therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness.To address this limitation,our focus was on CD132,a subunit common to six inflammatory factor receptors implicated in SLE.Our study revealed heightened CD132 expression in SLE patients’lymphocytes,contributing to the production of pro-inflammatory cytokines and immunoglobulins.We developed a novel humanized anti-CD132 monoclonal antibody,named as 2D4.2D4 efficiently blocked IL-21 and IL-15,with limited effectiveness against IL-2,thereby suppressing T and B cells without disrupting immune tolerance.In the mouse immunization model,2D4 virtually inhibited T cell-dependent,antigen-specific B-cell response.In lupus murine models,2D4 mitigated inflammation by suppressing multiple pro-inflammatory cytokines and anti-dsDNA antibody titers,also diminishing proteinuria and glomerulonephritis.Compared to Belimumab,2D4 exhibited superior efficacy in ameliorating the inflammatory state and preserving renal function.Moreover,2D4 exhibited the ability to inhibit the production of pro-inflammatory factors and autoantibodies in PBMCs from individuals with SLE,highlighting its therapeutic potential for SLE individuals.Potent,2D4 has the potential to significantly improve clinical outcomes in SLE and other complex autoimmune disorders.展开更多
基金CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2021-I2M-1-059)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2020-RC320-003)+1 种基金the National Natural Science Foundation of China(No.81830097)Special Program of National Natural Science Foundation of China(No.32141004).
文摘Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity.Genetics and environmental factors may contribute to the development of these autoimmune disorders.Although the etiology and pathogenesis of these disorders are poorly understood,environmental variables that induce aberrant epigenetic regulations may provide some insights.Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences.The most important epigenetic mechanisms are DNA methylation,histone modification,and noncoding RNAs.In this review,we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders,including systemic lupus erythematosus,bullous skin diseases,psoriasis,and systemic sclerosis.These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.
基金supported by the National Natural Science Foundation of China(grant number 81871695).
文摘Outer membrane vesicles(OMVs)are spherical particles shed from the outer membrane of Gram-negative bacteria,which contain the typical components present in the outer membrane,although enrichment of specific molecules may occur,and furthermore a variety of periplasmic components and occasionally some inner membrane or cytoplasmic fractions.Although the detailed mechanisms of OMV biogenesis are not fully illuminated yet,several models have been proposed that demonstrate OMV biogenesis is an orchestrated well-regulated process.OMV secretion offers a way for both intra-and inter-species bacterial communication and for interaction or modulation of the bacterial environment.Therefore,OMVs have proven to be functionally versatile and important for bacterial physiology and survival of the host environment.In the host,OMVs are internalized via host cell endocytosis pathways,allowing them to subsequently trigger a variety of cellular responses.In this review,we discuss the recent advances in establishing the mechanisms involved in OMV biogenesis and the impact of OMVs on bacterial physiology and intracellular modulation of the host.
基金supported by following fundings:the National Key R&D Program of China(No.2022YFC3601800)the CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-059)+4 种基金non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2021-RC320-001,No.2020-RC320-003)the Special Program of National Natural Science Foundation of China(NO.32141004)the Special Research Fund for Central Universities,Peking Union Medical College(No.3332023075)Natural Science Foundation of Jiangsu Province(No.BK20230130)National Natural Science Foundation of China(No.82302982).
文摘Current therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness.To address this limitation,our focus was on CD132,a subunit common to six inflammatory factor receptors implicated in SLE.Our study revealed heightened CD132 expression in SLE patients’lymphocytes,contributing to the production of pro-inflammatory cytokines and immunoglobulins.We developed a novel humanized anti-CD132 monoclonal antibody,named as 2D4.2D4 efficiently blocked IL-21 and IL-15,with limited effectiveness against IL-2,thereby suppressing T and B cells without disrupting immune tolerance.In the mouse immunization model,2D4 virtually inhibited T cell-dependent,antigen-specific B-cell response.In lupus murine models,2D4 mitigated inflammation by suppressing multiple pro-inflammatory cytokines and anti-dsDNA antibody titers,also diminishing proteinuria and glomerulonephritis.Compared to Belimumab,2D4 exhibited superior efficacy in ameliorating the inflammatory state and preserving renal function.Moreover,2D4 exhibited the ability to inhibit the production of pro-inflammatory factors and autoantibodies in PBMCs from individuals with SLE,highlighting its therapeutic potential for SLE individuals.Potent,2D4 has the potential to significantly improve clinical outcomes in SLE and other complex autoimmune disorders.
