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

Perona-Wright, G. , Jenkins, S. J., O'Connor, R. A., Zienkiewicz, D., McSorley, H. J., Maizels, R. M. , Anderton, S. M. and MacDonald, A. S. (2009) A pivotal role for CD40-mediated IL-6 production by dendritic cells during IL-17 induction in vivo. Journal of Immunology, 182(5), pp. 2808-2815. (doi: 10.4049/jimmunol.0803553) (PMID:19234175)

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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-γ. 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maizels, Professor Rick and Perona-Wright, Dr Georgia
Authors: Perona-Wright, G., Jenkins, S. J., O'Connor, R. A., Zienkiewicz, D., McSorley, H. J., Maizels, R. M., Anderton, S. M., and MacDonald, A. S.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:20 February 2009

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