SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation.
Publication Title
Science
Document Type
Article
Publication Date
8-21-2020
Keywords
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
Abstract
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.
Specialty/Research Institute
Institute for Systems Biology
