IL-21 promotes late activator APC-mediated T follicular helper cell differentiation in experimental pulmonary virus infection.
PLoS One
; 9(9): e105872, 2014.
Article
em En
| MEDLINE
| ID: mdl-25251568
ABSTRACT
IL-21 is a type-I cytokine that has pleiotropic immuno-modulatory effects. Primarily produced by activated T cells including NKT and TFH cells, IL-21 plays a pivotal role in promoting TFH differentiation through poorly understood cellular and molecular mechanisms. Here, employing a mouse model of influenza A virus (IAV) infection, we demonstrate that IL-21, initially produced by NKT cells, promotes TFH differentiation by promoting the migration of late activator antigen presenting cell (LAPC), a recently identified TFH inducer, from the infected lungs into the draining lymph nodes (dLN). LAPC migration from IAV-infected lung into the dLN is CXCR3-CXCL9 dependent. IL-21-induced TNF-α production by conventional T cells is critical to stimulate CXCL9 expression by DCs in the dLN, which supports LAPC migration into the dLN and ultimately facilitates TFH differentiation. Our results reveal a previously unappreciated mechanism for IL-21 modulation of TFH responses during respiratory virus infection.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Interleucinas
/
Linfócitos T Auxiliares-Indutores
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Infecções por Orthomyxoviridae
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Pneumopatias
/
Células Apresentadoras de Antígenos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article