Journal of Translational Medicine | |
Endogenous interleukin-10 constrains Th17 cells in patients with inflammatory bowel disease | |
Weiping Zou1  Jingyuan Fang4  Yanwei Lin4  John Kao3  Emina Huang2  Ilona Kryczek2  Shuang Wei2  Lin Wang2  Cailin M Wilke2  | |
[1] Graduate Program in Cancer Biology, Ann Arbor, MI, USA;Department of Surgery, University of Michigan, Ann Arbor, MI, USA;Department of Medicine, University of Michigan, Ann Arbor, MI, USA;Department of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, P. R. China | |
关键词: Crohn's disease; inflammation; IL-17; IL-1; IL-10; Th17; | |
Others : 1207801 DOI : 10.1186/1479-5876-9-217 |
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received in 2011-08-11, accepted in 2011-12-16, 发布年份 2011 | |
【 摘 要 】
Background
Th17 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 methods
We 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.
Results
We 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.
Conclusions
Endogenous 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】
2011 Wilke et al; licensee BioMed Central Ltd.
【 预 览 】
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