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Kidney GATA3^(+) regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury

Cellular & Molecular Immunology 2021年第5期18卷 1249-1261页

作者： Ryota Sakai Minako Ito Kyoko Komai Mana Iizuka-Koga Kazuhiko Matsuo Takashi Nakayama osamu Yoshie Koichi Amano Hiroshi Nishimasu osamu nureki Masato Kubo Akihiko Yoshimura Department of Microbiology and Immunology Keio University School of Medicine35 ShinanomachiShinjuku-kuTokyo160-8582Japan Department of Rheumatology and Clinical Immunology Saitama Medical CenterSaitama Medical University1981 KamodaKawagoe350-8550Japan Medical Institute of Bioregulation Kyushu University 3-1-1 MaidashiHigashi-kuFukuoka812-8582Japan Division of Chemotherapy Kindai University Faculty of PharmacyHigashi-Osaka577-8502Japan The Health and Kampo Institute SendaiMiyagi981-3205Japan Department of Biological Science Graduate School of ScienceThe University of Tokyo7-3-1 HongoBunkyo-kuTokyo113-0033Japan Center for Animal Disease Models Research Institute for Biomedical ScienceTokyo University of Science2669 YamazakiNoda-shiChiba278-0022Japan

FoxP3^(+)regulatory T cells(Tregs)play crucial roles in peripheral immune *** addition,Tregs that reside or accumulate in nonlymphoid tissues,called tissue Tregs,exhibit tissue-specific functions and contribute to the maintenance of tissue homeostasis and *** an experimental mouse model of crescentic glomerulonephritis induced by an anti-glomerular basement membrane antibody,Tregs started to accumulate in the kidney on day 10 of disease onset and remained at high levels(~30–35%of CD4^(+)T cells)during the late stage(days 21–90),which correlated with stable disease *** depletion on day 21 resulted in the relapse of renal dysfunction and an increase in Th1 cells,suggesting that Tregs are essential for disease control during the convalescence *** Tregs that accumulated in the kidney showed tissue Treg phenotypes,including high expression of GATA3,ST2(the IL33 receptor subunit),amphiregulin(Areg),and PPARγ.Although T-bet^(+) Tregs and RORγt^(+) Tregs were observed in the kidney,GATA3^(+) Tregs were predominant during the convalescence stage,and a PPARγagonist enhanced the accumulation of GATA3^(+) Tregs in the *** understand the function of specific genes in kidney Tregs,we developed a novel T cell transfer system to T cell-deficient *** experiment demonstrates that ST2,Areg,and CCR4 in Tregs play important roles in the accumulation of GATA3^(+) Tregs in the kidney and in the amelioration of renal *** data suggest that GATA3 is important for the recruitment of Tregs into the kidney,which is necessary for convalescence after renal tissue destruction.

关键词： Tissue Tregs autoantibody GATA3 kidney IL-33

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