TOX deficiency facilitates the differentiation of IL-17A-producingγδT cells to drive autoimmune hepatitis  

作　　者：Qifeng He Yijun Lu Wenfang Tian Runqiu Jiang Weiwei Yu Yong Liu Meiling Sun Fei Wang Haitian Zhang Ning Wu Zhongjun Dong Beicheng Sun 

机构地区：[1]Department of Hepatobiliary Surgery,Affiliated Drum Tower Hospital,Medical School of Nanjing University,Nanjing,China [2]Department of Hepatobiliary Surgery,The First Affiliated Hospital of Anhui Medical University,Hefei,China

出　　处：《Cellular & Molecular Immunology》2022年第10期1102-1116,共15页中国免疫学杂志（英文版）

基　　金：This work was supported by grants from the State Key Program of the National Natural Science Foundation(81930086 and 82120108012 to BS,82073157 and 81600487 to WT);the Science and Technology Project of Jiangsu Province(BE2018603 to BS);the Postgraduate Innovative Research Program of Jiangsu Province(KYCX20_0047 to QH).

摘　　要：The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poorly clarified.Here,we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation,promoted thymic IL-17A-producingγδT-cell(Tγδ17)lineage commitment,and led to the development of fatal autoimmune hepatitis(AIH)via different mechanisms.Transfer ofγδT cells from TOX-deficient mice reproduced AIH.TOX interacted with and stabilized the TCF1 protein to maintain the balance ofγδT-cell development in thymic progenitors,and overexpression of TCF1 normalizedαβ/γδlineage specification and activation.In addition,TOX expression was downregulated inγδT cells from AIH patients and was inversely correlated with the AIH diagnostic score.Our findings suggest multifaceted roles of TOX in autoimmune control involving mTEC and Tγδ17 development and provide a potential diagnostic marker for AIH.

关 键 词：Autoimmune hepatitis γδT cell IL-17A Immune tolerance TOX 

分 类 号：R575.1[医药卫生—消化系统]