期刊
JOURNAL OF IMMUNOLOGY
卷 182, 期 5, 页码 2808-2815出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803553
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资金
- Medical Research Council U.K.
- Wellcome Trust
- MRC [G0801924, G120/822] Funding Source: UKRI
- Medical Research Council [G120/822, G0801924, G9900991B] Funding Source: researchfish
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. The Journal of Immunology, 2009, 182: 2808-2815.
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