SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation

doi:10.1126/science.aba6652

GSTDTAP > 气候变化

DOI	10.1126/science.aba6652
	SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation
	Xin Wu; Yun Wang; Rui Huang; Qujing Gai; Haofei Liu; Meimei Shi; Xiang Zhang; Yonglin Zuo; Longjuan Chen; Qiwen Zhao; Yu Shi; Fengchao Wang; Xiaowei Yan; Huiping Lu; Senlin Xu; Xiaohong Yao; Lin Chen; Xia Zhang; Qiang Tian; Ziyan Yang; Bo Zhong; Chen Dong; Yan Wang; Xiu-Wu Bian; Xindong Liu
	2020-08-21
发表期刊	Science
出版年	2020
英文摘要	T follicular helper (TFH) cells are CD4+ T cells that facilitate B cell antibody production and B cell memory responses in the germinal centers (GCs) of lymphoid organs. These activities are in turn restrained by T follicular regulatory (TFR) cells, a population of T cells with unclear origins. Wu et al. now demonstrate that a subpopulation of TFH cells and fibroblastic reticular cells both produce sclerostin domain-containing protein 1 (SOSTDC1), which drives TFR cell generation by inhibiting Wnt–β-catenin signaling. In mice lacking the gene Sostdc1 , TFR cell numbers were substantially decreased and GC responses were enhanced. These insights into TFR cell biology and GC regulation may have important implications for autoantibody-mediated diseases and the future development of vaccines and therapies for autoimmune disease. Science , this issue p. [984][1] Germinal center (GC) responses potentiate the generation of follicular regulatory T (TFR) cells. However, the molecular cues driving TFR cell formation remain unknown. Here, we show that sclerostin domain-containing protein 1 (SOSTDC1), secreted by a subpopulation of follicular helper T (TFH) cells and T–B cell border–enriched fibroblastic reticular cells, is developmentally required for TFR cell generation. Fate tracking and transcriptome assessment in reporter mice establishes SOSTDC1-expressing TFH cells as a distinct T cell population that develops after SOSTDC1– TFH cells and loses the ability to help B cells for antibody production. Notably, Sostdc1 ablation in TFH cells results in substantially reduced TFR cell numbers and consequently elevated GC responses. Mechanistically, SOSTDC1 blocks the WNT–β-catenin axis and facilitates TFR cell differentiation. [1]: /lookup/doi/10.1126/science.aba6652
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/291220
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Xin Wu,Yun Wang,Rui Huang,et al. SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation[J]. Science,2020.
APA	Xin Wu.,Yun Wang.,Rui Huang.,Qujing Gai.,Haofei Liu.,...&Xindong Liu.(2020).SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation.Science.
MLA	Xin Wu,et al."SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation".Science (2020).