Chemokine CXCL11 links microbial stimuli to intestinal inflammation

Z Liu

X Chen

X Wang

X Chen

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^{Department of Gastroenterology, the Tenth People's Hospital of Shanghai, Tongji University, Shanghai}

^{Department of Forensic Pathology, Huazhong University of Science and Technology, Wuhan, China}

^{Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada}

P.-C. Yang, Room T3303, 50 Charlton Avenue East, St Joseph Hospital, Hamilton, ON, Canada L8N 4A6. E-mail: ac.retsamcm@pgnay

^{These authors contributed equally to this study.}

Accepted 2011 Feb 21.

Abstract

Interleukin (IL)-17 plays an important role in the pathogenesis in a number of immune inflammatory disorders. This study aims to investigate the mechanism by which microbial product flagellin is involved in the development of T helper type (Th)17 cells. Serum levels of IL-17 and CXCL9-11 in patients with ulcerative colitis (UC) were evaluated. The source and mechanism of CXC11 release in intestinal mucosa were examined with colonic biopsies from UC patients and a colitis mouse model. The role of flagellin in the development of Th17 cells was studied with a cell co-culture system. High serum levels of CXCL11 and IL-17 were observed in UC. Flagellin could induce the production of CXCL11 in CD14^{cells that facilitated the development of Th17 cells. In a skewed Th1 response environment flagellin induces intestinal inflammation, with IL-17 expression predominant. CXCR3/CXCL11 pathway is involved in microbial product flagellin-induced intestinal inflammation in which the Th17 response plays an important role.}

Keywords: flagellin, inflammatory bowel disease, intestine, Th17 cells

Abstract

Acknowledgments

This study was supported by grants from the Canadian Institute of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC) and the Natural Science Foundation of China (no. 30770988, 30971358). Dr P.-C. Yang holds a New Investigator Award of CIHR.

Acknowledgments

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