A pivotal role for CD40-mediated IL-6 production by dendritic cells during IL-17 induction in vivo

J Immunol. 2009 Mar 1;182(5):2808-15. doi: 10.4049/jimmunol.0803553.


The costimulatory requirements for Th17 development remain to be defined. In this study, we show that CD40-deficient animals immunized with the gram-positive bacterium Propionibacterium acnes were specifically impaired in their ability to mount an IL-17 response, but not that of IFN-gamma. The same cytokine imbalance resulted from in vivo priming with pathogen-pulsed, CD40-deficient dendritic cells (DC). Engagement of CD40 on P. acnes-conditioned DC stimulated the release of IL-12, IL-23, and IL-6, of which IL-6 alone proved essential for Th17 differentiation. Compared with wild-type DC, priming with those lacking expression of CD40 resulted in reduced disease severity during experimental autoimmune encephalomyelitis, coincident with reduced IL-17 production. Our data delineate sequential requirements for DC expression of CD40 and production of IL-6 during Th17 polarization in vitro and in vivo, and reveal distinct costimulatory requirements for Th1 vs Th17 generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD40 Antigens / deficiency
  • CD40 Antigens / genetics
  • CD40 Antigens / physiology*
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Dendritic Cells / microbiology
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / metabolism
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / deficiency
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Molecular Sequence Data
  • Propionibacterium acnes / immunology
  • Salmonella typhimurium / immunology


  • CD40 Antigens
  • Interleukin-17
  • Interleukin-6