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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number217
JournalJournal of Translational Medicine
Volume9
Issue number1
DOIs
StatePublished - Dec 16 2011
Externally publishedYes

Keywords

  • Crohn's disease
  • Il-1
  • Il-10
  • Il-17
  • Inflammation
  • Th17

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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