Tumor necrosis factor-like cytokine 1A plays a role in inflammatory bowel disease pathogenesis.
Proc Natl Acad Sci U S A
; 120(34): e2120771120, 2023 08 22.
Article
em En
| MEDLINE
| ID: mdl-37579137
ABSTRACT
The binding of tumor necrosis factor-like cytokine 1A (TL1A) to death receptor 3 (DR3) plays an important role in the interaction between dendritic cells (DCs) and T cells and contributes to intestinal inflammation development. However, the mechanism by which DCs expressing TL1A mediate helper T (Th) cell differentiation in the intestinal lamina propria (LP) during the pathogenesis of inflammatory bowel disease remains unclear. In this study, we found that TL1A/DR3 promoted Th1 and Th17 cell differentiation in T-T and DC-T cell interaction-dependent manners. TL1A-deficient CD4+ T cells failed to polarize into Th1/Th17 cells and did not cause colonic inflammation in a T cell transfer colitis model. Notably, TL1A was located in the cytoplasm and nuclei of DCs, positively regulated the DC-specific ICAM-grabbing nonintegrin/RAF1/nuclear factor κB signaling pathway, enhanced the antigen uptake ability of DCs, and promoted TLR4-mediated DC activation, inducing naive CD4+ T cell differentiation into Th1 and Th17 cells. Our work reveals that TL1A plays a regulatory role in inflammatory bowel disease pathogenesis.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
/
Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article