SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation.
Adaptor Proteins, Signal Transducing; Animals; B-Lymphocytes; Cell Differentiation; Germinal Center; Lymphocyte Activation; Lymphocyte Count; Mice; Mice, Mutant Strains; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Wnt Proteins; beta Catenin
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.
Institute for Systems Biology
Wu, Xin; Wang, Yun; Huang, Rui; Gai, Qujing; Liu, Haofei; Shi, Meimei; Zhang, Xiang; Zuo, Yonglin; Chen, Longjuan; Zhao, Qiwen; Shi, Yu; Wang, Fengchao; Yan, Xiaowei; Lu, Huiping; Xu, Senlin; Yao, Xiaohong; Chen, Lin; Zhang, Xia; Tian, Qiang; Yang, Ziyan; Zhong, Bo; Dong, Chen; Wang, Yan; Bian, Xiu-Wu; and Liu, Xindong, "SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation." (2020). Articles, Abstracts, and Reports. 3514.