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

Journal of Translational Medicine

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

 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.

【 图 表 】

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