SOSTDC1-producing follicular helper T cells promote regulatory follicular T cell differentiation.
Science
; 369(6506): 984-988, 2020 08 21.
Article
em En
| MEDLINE
| ID: mdl-32820125
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-ß-catenin axis and facilitates TFR cell differentiation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
/
Linfócitos T Auxiliares-Indutores
/
Proteínas Adaptadoras de Transdução de Sinal
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article