TY - JOUR
T1 - A pivotal role for CD40-mediated IL-6 production by dendritic cells during IL-17 induction in vivo
AU - Perona-Wright, Georgia
AU - Jenkins, Stephen J.
AU - O'Connor, Richard A.
AU - Zienkiewicz, Dimitrios
AU - McSorley, Henry J.
AU - Maizels, Rick M.
AU - Anderton, Stephen M.
AU - MacDonald, Andrew S.
N1 - , Medical Research Council, United Kingdom, Wellcome Trust, United Kingdom
PY - 2009/3/1
Y1 - 2009/3/1
N2 - 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 pathogenpulsed, 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. Copyright © 2009 by The American Association of Immunologists, Inc.
AB - 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 pathogenpulsed, 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. Copyright © 2009 by The American Association of Immunologists, Inc.
U2 - 10.4049/jimmunol.0803553
DO - 10.4049/jimmunol.0803553
M3 - Article
C2 - 19234175
SN - 1550-6606
VL - 182
SP - 2808
EP - 2815
JO - Journal of Immunology
JF - Journal of Immunology
IS - 5
ER -