Blocking of IL-6 signaling pathway prevents CD4� T cell-mediated colitis in a T(h)17-independent manner

Abstract

Naive CD41 T cells rapidly proliferate to generate effector cells after encountering an antigen and small numbers survive as memory T cells in preparation for future immunological events. In the present work, adoptive transfer of naive CD41 T cells into RAG22/2 mice caused the generation of memory-type effector T cells including Th1, Th2, Th17 and regulatory T cells, and eventually induced T cell-dependent colitis. We found here that blocking of the IL-6R with a specific mAb remarkably inhibited the CD41 T cell-mediated colitis in parallel with the inhibition of Th17 cell generation. However, the transfer of naive CD41 T cells prepared from IL-172/2mice still induced severe colitis. At the effector phase, the mAb significantly inhibited IL-17 but not IFN-g production. The blockade of IL-6 signaling enhanced the generation of IL-4- and IL-10-producing CD41 T cells, and inhibited up-regulation of tumor necrosis factor-a mRNA expression in the colon. These findings clearly demonstrated that IL-6 is a critical factor for the induction of colitis by expansion of naive CD41 T cells in RAG22/2 mice. Thus, the IL-6-mediated signaling pathway may be a significant therapeutic target in T cell-mediated autoimmune diseases