生发中心
FOXP3型
细胞生物学
细胞生长
B细胞
CXCR5型
化学
生物
免疫学
抗体
免疫系统
生物化学
作者
S. Kawano,Hiroki Mitoma,Shoichiro Inokuchi,Yusuke Yamauchi,Keiichi Yokoyama,Jumpei Nogami,Yuichiro Semba,Masahiro Ayano,Yasutaka Kimoto,Mitsuteru Akahoshi,Nobuyuki Ono,Yojiro Arinobu,Koichi Akashi,Takahiko Horiuchi,Hiroaki Niiro
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2022-03-01
卷期号:208 (5): 1057-1065
被引量:6
标识
DOI:10.4049/jimmunol.2100323
摘要
T follicular regulatory (Tfr) cells are a subset of CD4+ T cells that express CXCR5 and migrate into germinal centers (GCs). They regulate GC reactions by communicating with T follicular helper (Tfh) and B cells. TNF inhibitors are used in inflammatory diseases; however, the generation of autoantibodies or anti-drug Abs sometimes causes problems. Because TNFR2 signaling is important for suppressive functions of regulatory T cells, we investigated the role of TNFR2 on human Tfr cells. Tfr cells stimulated with MR2-1 (an anti-TNFR2 agonistic Ab) were analyzed for cell proliferation, Foxp3 expression, and surface molecules. Tfh/B cell proliferation, IgM production, and differentiation in cocultures with MR2-1-stimulated Tfr cells were examined. Tfr cells express a high level of TNFR2. MR2-1 stimulation altered the gene expression profile of Tfr cells. Cell proliferation and Foxp3 expression of Tfr cells were enhanced by MR2-1. MR2-1-stimulated Tfr cells expressed ICOS and Programmed cell death protein 1 and significantly suppressed Tfh/B cell proliferation, IgM production, and B cell differentiation. TNFR2-stimulated Tfr cells retained the migration function according to the CXCL13 gradient. In conclusion, we showed that TNFR2-stiumulated Tfr cells can regulate Tfh and B cells. Aberrant antibody production during TNF inhibitor treatment might be, at least in part, associated with TNFR2 signaling inhibition in Tfr cells. In addition, expansion and maturation of Tfr cells via TNFR2 stimulation in vitro may be useful for a cell-based therapy in inflammatory and autoimmune diseases to control GC reactions.
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