SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation
Xin Wu, Yun Wang, Yun Wang, Rui Huang, Qu‐Jing 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, Yan Wang, Xiu‐Wu Bian, Xindong Liu
Abstract
SOSTDC1 for germinal center regulation T follicular helper (T FH ) 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 (T FR ) cells, a population of T cells with unclear origins. Wu et al. now demonstrate that a subpopulation of T FH cells and fibroblastic reticular cells both produce sclerostin domain-containing protein 1 (SOSTDC1), which drives T FR cell generation by inhibiting Wnt–β-catenin signaling. In mice lacking the gene Sostdc1 , T FR cell numbers were substantially decreased and GC responses were enhanced. These insights into T FR 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