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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2011

Open Access 01-12-2011 | Research

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

Authors: Cailin M Wilke, Lin Wang, Shuang Wei, Ilona Kryczek, Emina Huang, John Kao, Yanwei Lin, Jingyuan Fang, Weiping Zou

Published in: Journal of Translational Medicine | Issue 1/2011

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Abstract

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.
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Metadata
Title
Endogenous interleukin-10 constrains Th17 cells in patients with inflammatory bowel disease
Authors
Cailin M Wilke
Lin Wang
Shuang Wei
Ilona Kryczek
Emina Huang
John Kao
Yanwei Lin
Jingyuan Fang
Weiping Zou
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2011
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-9-217

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