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第十届全国免疫学学术大会

作者： Jian Gu Jie Zhao Xuhao Ni Hao Lu Yunjie Lu Kunpeng Wang Zhou Bo Ling Lu Nanjing Medical University

Autoimmune diseases are characterized by an imbalance between regulatory T(Treg)cells and effector T cell subsets such as Th1 and Th17 *** studies have demonstrated that thymus-derived naturally-occurring CD4+Foxp3+regulatory T cells(n Tregs)in both human and mouse are unstable and dysfunctional in the presence of pro-inflammatory *** this study,human CD39hi n Tregs and CD39low n Tregs were sorted from n Tregs 10 days after ***3 expression and suppressive activities were analyzed in vitro and in vivo using a standard assay in a humanized animal *** find that in the presence of IL-1βand IL-6,CD4+CD39hi n Treg were stable,while CD4+CD39low n Tregs lose Foxp3 expression and transdifferentiate into Th1 or Th17 ***,human CD4+CD39hi n Treg,but not CD4+CD39low n Treg significantly protect xeno-graft versus host diseases(x gvhd)and only these cells maintained functional activity against x ***,STAT1 and STAT3 activation and CPG methylation were evaluated in CD39lown Tregs under pathological *** results strongly implicated the physiological importance of CD39 expression in maintaining Foxp3 stability,and suggest that CD39hi n Tregs may represent a novel treatment strategy to control established chronic immune-mediated autoimmune and inflammatory diseases.

关键词： nTreg CD39 xeno-gvhd Foxp3

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Human CD39hi regulatory T cells present stronger stability and function under inflammatory conditions

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Cellular & Molecular Immunology 2017年第6期14卷 521-528页

作者： Jian Gu Xuhao Ni Xiongxiong Pan Hao Lu Yunjie Lu Jie Zhao Song Guo Zheng Keli L Hippen Xuehao Wang Ling Lu Translational Medicine Research Center Affiliated Jiangning Hospital and Liver Transplantation Center First Affiliated Hospital Nanjing Medical University Nanjing 210029 China University of Minnesota Cancer Center and Division of Bone Marrow Transplantation Department of Pediatrics University of Minnesota Minneapolis MN 55455 USA Division of Rheumatology Penn State Milton S. Hershey Medical Center Hershey PA 17033 USA

Autoimmune diseases are characterized by an imbalance between regulatory T cells and effector T-cell subsets, such as Thl and Th17 cells. Studies have confirmed that natural CD4＋Foxp3＋ Tregs were unstable and dysfunctional in the presence of pro-inflammatory cytokines. In the current study, human CD39hi Tregs and CD39low Tregs were sorted from Tregs in vitro after 7 days of expansion. The functions of both Treg subsets were investigated under inflammatory conditions in vitro and in vivo. In the presence of IL-1β and IL-6, cultured CD4＋CD39hi Tregs maintained stable forkhead box protein 3 expression, whereas CD4＋CD39low Tregs lost Foxp3 expression and trans-differentiated into Thl or Th17 cells. Decreased IL-1βR and IL-6R expression on the CD39hi Tregs was the primary mechanism responsible for Treg stability. In addition, reduced activation of downstream molecules, such as STAT1 and STAT3, through the modulation of CpG demethylation played an important role. Finally, human CD4＋CD39hi Tregs but not CD4＋CD39low Tregs protected against xenograft versus host disease in model mice. These results strongly implied the physiological importance of CD39 expression and suggested that manipulation of CD39hi Tregs might represent a novel strategy for the treatment of autoimmune diseases.

关键词： CD39 stability Tregs xeno-gvhd

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