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 |
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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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