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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adjuvants, Immunologic
  • Animals
  • Antibody Formation / immunology
  • CARD Signaling Adaptor Proteins
  • Candida albicans / immunology
  • Cell Differentiation
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Immunity, Innate / immunology*
  • Interleukin-17 / biosynthesis*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lectins, C-Type
  • Membrane Proteins / agonists
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Syk Kinase
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Adjuvants, Immunologic
  • CARD Signaling Adaptor Proteins
  • Card9 protein, mouse
  • Interleukin-17
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • dectin 1
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse