IL-27, targeting antigen-presenting cells, promotes Th17 differentiation and colitis in mice

T helper type 17 (Th17) cells have been implicated in autoimmunity and inflammatory bowel disease (IBD). Antigen-presenting cell (APC) -derived cytokines such as interleukin (IL)-1 beta and IL-6 are key mediators supporting Th17 differentiation, yet how these factors are induced in vivo remains unclear. Here, we show that IL-27 acting on APCs enhances IL-6 and IL-1 beta production and Th17 differentiation. IL-27R alpha-/- T-cell receptor (TCR)beta-/- recipients fail to develop gut inflammation following naive CD4 T-cell transfer, whereas IL-27R alpha+/+ TCR beta-/- recipients develop severe colitis. Investigation of T-cell responses exhibits that IL-27R alpha-/- TCR beta-/- mice do not support Th17 differentiation with significantly decreased levels of IL-6 and IL-1 beta by APCs. Our study has identified a novel proinflammatory role for IL-27 in vivo that promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs.