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

Georgia Perona-Wright, Stephen J Jenkins, Richard A O'Connor, Dimitrios Zienkiewicz, Henry J McSorley, Rick M Maizels, Stephen M Anderton, Andrew S MacDonald

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)2808-15
Number of pages8
JournalJournal of Immunology
Volume182
Issue number5
DOIs
Publication statusPublished - Mar 2009

Keywords

  • Amino Acid Sequence
  • Animals
  • Antigens, CD40
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells
  • Encephalomyelitis, Autoimmune, Experimental
  • Interleukin-17
  • Interleukin-6
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Molecular Sequence Data
  • Propionibacterium acnes
  • Salmonella typhimurium

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