Artigo Acesso aberto Revisado por pares

Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17

2007; Nature Portfolio; Volume: 8; Issue: 6 Linguagem: Inglês

10.1038/ni1460

ISSN

1529-2916

Autores

Salomé LeibundGut‐Landmann, Olaf Groß, Matthew J. Robinson, Fabiola Osorio, Emma Slack, S. Vicky Tsoni, Edina Schweighoffer, Victor L. J. Tybulewicz, Gordon D. Brown, Jürgen Ruland, Caetano Reis e Sousa,

Tópico(s)

Immunotherapy and Immune Responses

Resumo

The C-type lectin dectin-1 binds to yeast and signals through the kinase Syk and the adaptor CARD9 to induce production of interleukin 10 (IL-10) and IL-2 in dendritic cells (DCs). However, whether this pathway promotes full DC activation remains unclear. Here we show that dectin-1–Syk–CARD9 signaling induced DC maturation and the secretion of proinflammatory cytokines, including IL-6, tumor necrosis factor and IL-23, but little IL-12. Dectin-1-activated DCs 'instructed' the differentiation of CD4+ IL-17-producing effector T cells (TH-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of TH-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent TH-17 responses to the organism. Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of TH-17 responses to some pathogens.

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