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

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 

机构地区：[1]Department of Microbiology and Immunology,Keio University School of Medicine,35 Shinanomachi,Shinjuku-ku,Tokyo,160-8582,Japan [2]Department of Rheumatology and Clinical Immunology,Saitama Medical Center,Saitama Medical University,1981 Kamoda,Kawagoe,350-8550,Japan [3]Medical Institute of Bioregulation Kyushu University,3-1-1 Maidashi,Higashi-ku,Fukuoka,812-8582,Japan [4]Division of Chemotherapy,Kindai University Faculty of Pharmacy,Higashi-Osaka,577-8502,Japan [5]The Health and Kampo Institute,Sendai,Miyagi,981-3205,Japan [6]Department of Biological Science,Graduate School of Science,The University of Tokyo,7-3-1 Hongo,Bunkyo-ku,Tokyo,113-0033,Japan [7]Center for Animal Disease Models,Research Institute for Biomedical Science,Tokyo University of Science,2669 Yamazaki,Noda-shi,Chiba,278-0022,Japan

出　　处：《Cellular & Molecular Immunology》2021年第5期1249-1261,共13页中国免疫学杂志（英文版）

基　　金：supported by JSPS KAKENHI(S)JP17H06175,Challenging Research(P)JP18H05376;AMED-CREST JP 20gm1110009 grants to A.Y.;JSPS KAKENHI 17K15667,19H04817,and 19K16618,AMED-PRIME 20gm6210012,a research grant from the Kishimoto Foundation,the Tomizawa Jun-ichi&Keiko Fund of Molecular Biology Society of Japan for Young Scientist,a research grant for young investigators by The Mitsubishi Foundation to M.I.;by the Mochida Memorial Foundation for Medical and Pharmaceutical Research,the Takeda Science Foundation,the Uehara Memorial Foundation,the Naito Memorial Foundation,the Kanae Foundation,the SENSHIN Medical Research Foundation,the Astellas Foundation for Research on Metabolic Disorders,an Inoue Research Award,a Life Science Research Award,and Keio Gijuku Academic Developmental Funds.

摘　　要：FoxP3^(+)regulatory T cells(Tregs)play crucial roles in peripheral immune tolerance.In 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 repair.In 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 control.Treg 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 stage.The 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 kidney.To understand the function of specific genes in kidney Tregs,we developed a novel T cell transfer system to T cell-deficient mice.This 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 injury.Our 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 

分 类 号：R692[医药卫生—泌尿科学]