First Author | Perona-Wright G | Year | 2009 |
Journal | J Immunol | Volume | 182 |
Issue | 5 | Pages | 2808-15 |
PubMed ID | 19234175 | Mgi Jnum | J:146255 |
Mgi Id | MGI:3837093 | Doi | 10.4049/jimmunol.0803553 |
Citation | Perona-Wright G, et al. (2009) A pivotal role for CD40-mediated IL-6 production by dendritic cells during IL-17 induction in vivo. J Immunol 182(5):2808-15 |
abstractText | 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. |