Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis.
Nat Commun
; 9(1): 3555, 2018 09 03.
Article
em En
| MEDLINE
| ID: mdl-30177845
ABSTRACT
T-cells are crucial in maintanence of intestinal homeostasis, however, it is still unclear how microbiota metabolites regulate T-effector cells. Here we show gut microbiota-derived short-chain fatty acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptors 43 (GPR43). Microbiota antigen-specific Gpr43-/- CBir1 transgenic (Tg) Th1 cells, specific for microbiota antigen CBir1 flagellin, induce more severe colitis compared with wide type (WT) CBir1 Tg Th1 cells in Rag-/- recipient mice. Treatment with SCFAs limits colitis induction by promoting IL-10 production, and administration of anti-IL-10R antibody promotes colitis development. Mechanistically, SCFAs activate Th1 cell STAT3 and mTOR, and consequently upregulate transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1), which mediates SCFA-induction of IL-10. SCFA-treated Blimp1-/- Th1 cells produce less IL-10 and induce more severe colitis compared to SCFA-treated WT Th1 cells. Our studies, thus, provide insight into how microbiota metabolites regulate Th1 cell functions to maintain intestinal homeostasis.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Interleucina-10
/
Colite
/
Células Th1
/
Receptores Acoplados a Proteínas G
/
Ácidos Graxos Voláteis
/
Microbioma Gastrointestinal
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2018
Tipo de documento:
Article