The TNF-family ligand TL1A and its receptor DR3 promote T cell-mediated allergic immunopathology by enhancing differentiation and pathogenicity of IL-9-producing T cells.
J Immunol
; 194(8): 3567-82, 2015 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-25786692
ABSTRACT
The TNF family cytokine TL1A (Tnfsf15) costimulates T cells and type 2 innate lymphocytes (ILC2) through its receptor DR3 (Tnfrsf25). DR3-deficient mice have reduced T cell accumulation at the site of inflammation and reduced ILC2-dependent immune responses in a number of models of autoimmune and allergic diseases. In allergic lung disease models, immunopathology and local Th2 and ILC2 accumulation is reduced in DR3-deficient mice despite normal systemic priming of Th2 responses and generation of T cells secreting IL-13 and IL-4, prompting the question of whether TL1A promotes the development of other T cell subsets that secrete cytokines to drive allergic disease. In this study, we find that TL1A potently promotes generation of murine T cells producing IL-9 (Th9) by signaling through DR3 in a cell-intrinsic manner. TL1A enhances Th9 differentiation through an IL-2 and STAT5-dependent mechanism, unlike the TNF-family member OX40, which promotes Th9 through IL-4 and STAT6. Th9 differentiated in the presence of TL1A are more pathogenic, and endogenous TL1A signaling through DR3 on T cells is required for maximal pathology and IL-9 production in allergic lung inflammation. Taken together, these data identify TL1A-DR3 interactions as a novel pathway that promotes Th9 differentiation and pathogenicity. TL1A may be a potential therapeutic target in diseases dependent on IL-9.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
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Diferenciação Celular
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Interleucina-9
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Linfócitos T Auxiliares-Indutores
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Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral
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Membro 25 de Receptores de Fatores de Necrose Tumoral
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2015
Tipo de documento:
Article