title: Endogenous interleukin-10 constrains Th17 cells in patients with inflammatory bowel disease.
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.
  
  
  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.
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Cailin M
authors.initials: CM
authors.lastname: Wilke
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wei
authors.forename: Ilona
authors.initials: I
authors.lastname: Kryczek
authors.forename: Emina
authors.initials: E
authors.lastname: Huang
authors.forename: John
authors.initials: J
authors.lastname: Kao
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Lin
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Fang
authors.forename: Weiping
authors.initials: W
authors.lastname: Zou
mesh_terms: D000818:Animals; D003424:Crohn Disease / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D018836:Inflammation Mediators; D007375:Interleukin-1; D020381:Interleukin-17; D017472:Receptors, Interleukin-1; D016753:Interleukin-10