Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
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DOI：
10.1038/ni1460
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发表时间：
2007-06-01
影响因子：
30.5
通讯作者：
Sousa, Caetano Reis e
中科院分区：
文献类型：
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作者：
LeibundGut-Landmann, Salome;Gross, Olaf;Sousa, Caetano Reis e
c型凝集素dectin-1与酵母结合，通过激酶Syk和接头CARD9发出信号，诱导树突状细胞（DCs）产生白细胞介素10 （IL-10）和IL-2。然而，该通路是否促进DC完全激活尚不清楚。本研究表明，dectin-1-Syk-CARD9信号通路诱导DC成熟和促炎细胞因子的分泌，包括IL-6、肿瘤坏死因子和IL-23，但IL-12很少。dectin-1激活的dc在体外“指示”CD4+产生il -17的效应T细胞（TH-17细胞）的分化，dectin-1激动剂在体内作为促进TH-17和T辅助型1细胞分化的佐剂。感染白色念珠菌诱导card9依赖性TH-17对机体的应答。我们的数据表明，通过Syk和CARD9的信号可以独立于toll样受体信号将先天免疫与适应性免疫偶联，并且CARD9是TH-17对某些病原体反应的发展所必需的。
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.