Endogenous interleukin-10 constrains Th17 cells in patients with inflammatory bowel disease

Journal of Translational Medicine

Research

Jingyuan Fang¹  John Kao²  Lin Wang³  Emina Huang³  Shuang Wei³  Ilona Kryczek³  Yanwei Lin⁴  Cailin M Wilke⁵  Weiping Zou⁶ 

[1] Department of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, P. R, China;Department of Medicine, University of Michigan, Ann Arbor, MI, USA;Department of Surgery, University of Michigan, Ann Arbor, MI, USA;Department of Surgery, University of Michigan, Ann Arbor, MI, USA;Department of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, P. R, China;Department of Surgery, University of Michigan, Ann Arbor, MI, USA;Graduate Program in Immunology, University of Michigan, Ann Arbor, MI, USA;Department of Surgery, University of Michigan, Ann Arbor, MI, USA;Graduate Program in Immunology, University of Michigan, Ann Arbor, MI, USA;University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA;Graduate Program in Cancer Biology, Ann Arbor, MI, USA;

关键词: Th17;    IL-10;    IL-1;    IL-17;    inflammation;    Crohn's disease;   

DOI  :  10.1186/1479-5876-9-217

 received in 2011-08-11, accepted in 2011-12-16,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundTh17 cells play a role in inflammation. Interleukin (IL)-10 is a potent anti-inflammatory cytokine. However, it is poorly understood whether and how endogenous IL-10 impacts the development of Th17 cells in human pathologies.Materials and methodsWe examined the relationship between IL-10 and Th17 cells in patients with Crohn's disease and in IL-10-deficient (IL-10-/-) mice. Th17 cells and dendritic cells (DCs) were defined by flow cytometry and evaluated by functional studies.ResultsWe detected elevated levels of IL-17 and Th17 cells in the intestinal mucosa of patients with Crohn's disease. Intestinal DCs from Crohn's patients produced more IL-1β than controls and were superior to blood DCs in Th17 induction through an IL-1-dependent mechanism. Furthermore, IL-17 levels were negatively associated with those of IL-10 and were positively associated those of IL-1β in intestinal mucosa. These data point toward an in vivo cellular and molecular link among endogenous IL-10, IL-1, and Th17 cells in patients with Crohn's disease. We further investigated this relationship in IL-10-/- mice. We observed a systemic increase in Th17 cells in IL-10-/- mice when compared to wild-type mice. Similar to the intestinal DCs in patients with Crohn's disease, murine IL-10-/- DCs produced more IL-1β than their wild-type counterparts and promoted Th17 cell development in an IL-1-dependent manner. Finally, in vivo blockade of IL-1 receptor signaling reduced Th17 cell accumulation and inflammation in a mouse model of chemically-induced colitis.ConclusionsEndogenous IL-10 constrains Th17 cell development through the control of IL-1 production by DCs, and reaffirms the crucial anti-inflammatory role of IL-10 in patients with chronic inflammation.

【 授权许可】

Unknown   
© Wilke et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.