Endogenous interleukin-10 constrains Th17 cells in patients with inflammatory bowel disease
1 Department of Surgery, University of Michigan, Ann Arbor, MI, USA
2 Graduate Program in Immunology, University of Michigan, Ann Arbor, MI, USA
3 Department of Medicine, University of Michigan, Ann Arbor, MI, USA
4 Department of Medicine, Renji Hospital, Shanghai Jiao-Tong University, Shanghai, P. R. China
5 University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
6 Graduate Program in Cancer Biology, Ann Arbor, MI, USA
Journal of Translational Medicine 2011, 9:217 doi:10.1186/1479-5876-9-217Published: 16 December 2011
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.
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.
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.