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

S.-J. Zhang, L. Wang, L. Ming, X.-B. Guo, H.-M. Wang, X.-W. Li, L. Li

Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. wangleisea@126.com

 

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• Gastroenterology

BACKGROUND: Inflammatory bowel disease (IBD) is a common disease in human resulted from a various of factors including genetic background, immune system and environment factors.

OBJECTIVES: 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 regultory of IL-17 production in acute IBD model.

MATERIALS AND METHODS: Wildtype mice were treated with anti-IL-6 neutralizing antibodies to block IL-6 signal And then treated with DSS to induce acute IBD.

RESULTS: 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 conpared with control group. Our research suggested blockade of IL-6 signal pathways in acute colitus model resulted in specifical activation of IL-17 producing cell population. Furthermore, CD44+ activated Th17 cell popualtion and CD44- IL-17 producing T cells exhibited different susceptibility to IL-6 signal in our model.

CONCLUSIONS: 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.

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