LeibundGut-Landmann Salomé, Gross Olaf, Robinson Matthew J, Osorio Fabiola, Slack Emma C, Tsoni S Vicky, Schweighoffer Edina, Tybulewicz Victor, Brown Gordon D, Ruland Jürgen, Reis e Sousa Caetano
Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, UK.
Nat Immunol. 2007 Jun;8(6):630-8. doi: 10.1038/ni1460. Epub 2007 Apr 22.
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 (T(H)-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of T(H)-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent T(H)-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 T(H)-17 responses to some pathogens.
C型凝集素dectin-1可与酵母结合，并通过激酶Syk和衔接蛋白CARD9发出信号，从而在树突状细胞（DC）中诱导白细胞介素10（IL-10）和IL-2的产生。然而，该信号通路是否能促进DC的完全激活仍不清楚。在此我们表明，dectin-1-Syk-CARD9信号传导可诱导DC成熟以及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分泌较少。dectin-1激活的DC在体外“指导”了产生IL-17的CD4+效应T细胞（T(H)-17细胞）的分化，并且一种dectin-1激动剂在体内作为佐剂促进了T(H)-17和1型辅助性T细胞的分化。白色念珠菌感染可诱导机体产生依赖CARD9的T(H)-17反应。我们的数据表明，通过Syk和CARD9的信号传导可独立于Toll样受体信号将先天性免疫与适应性免疫联系起来，并且CARD9是对某些病原体产生T(H)-17反应所必需的。
Int J Mol Sci. 2025-5-21
Biomolecules. 2025-3-26
Nat Rev Microbiol. 2025-4-17
J Exp Med. 2025-6-2
Scand J Immunol. 2025-4
Front Immunol. 2025-2-21
Zotero 插件