Blockade of IL-6 signal exacerbates acute inflammatory bowel disease via inhibiting IL-17 producing in activated CD4+ Th17 population

Inflammatory bowel disease (IBD) is a common disease in human resulted from a various of factors including genetic background, immune system and environment factors.Recent studies suggest pro-inflammatory cytokine IL-17 producing cell subset was involved in the disease development and the maintenance of IBD. And the differentiated and activation of IL-17 producing cells were mostly dependent on the cytokines profile secreted by innate cells in intestinal tissues. In this study, we examined the functions of IL-6 signal in regulatory of IL-17 production in acute IBD model.Wildtype mice were treated with anti-IL-6 neutralizing antibodies to block IL-6 signal And then treated with DSS to induce acute IBD.Mice treated with anti-IL-6 neutralizing antibodies show severe colitis and high level of pro-inflammatory cytokine IL-17 production in DSS-induced acute IBD model when compared with control group. Our research suggested blockade of IL-6 signal pathways in acute colitus model resulted in specific activation of IL-17 producing cell population. Furthermore, CD44+ activated Th17 cell population and CD44- IL-17 producing T cells exhibited different susceptibility to IL-6 signal in our model.Blockade of IL-6 signal in DSS-induced acuted IBD model increased IL-17 production level specifically in CD44- T cells and reduced CD44+ Th17 cell population.