Cutting edge: IL-36 receptor promotes resolution of intestinal damage

O Medina-Contreras, A Harusato, H Nishio… - The journal of …, 2016 - journals.aai.org
The journal of immunology, 2016journals.aai.org
IL-1 family members are central mediators of host defense. In this article, we show that the
novel IL-1 family member IL-36γ was expressed during experimental colitis and human
inflammatory bowel disease. Germ-free mice failed to induce IL-36γ in response to dextran
sodium sulfate (DSS)-induced damage, suggesting that gut microbiota are involved in its
induction. Surprisingly, IL-36R–deficient (Il1rl2−/−) mice exhibited defective recovery
following DSS-induced damage and impaired closure of colonic mucosal biopsy wounds …
Abstract
IL-1 family members are central mediators of host defense. In this article, we show that the novel IL-1 family member IL-36γ was expressed during experimental colitis and human inflammatory bowel disease. Germ-free mice failed to induce IL-36γ in response to dextran sodium sulfate (DSS)-induced damage, suggesting that gut microbiota are involved in its induction. Surprisingly, IL-36R–deficient (Il1rl2−/−) mice exhibited defective recovery following DSS-induced damage and impaired closure of colonic mucosal biopsy wounds, which coincided with impaired neutrophil accumulation in the wound bed. Failure of Il1rl2−/− mice to recover from DSS-induced damage was associated with a profound reduction in IL-22 expression, particularly by colonic neutrophils. Defective recovery of Il1rl2−/− mice could be rescued by an aryl hydrocarbon receptor agonist, which was sufficient to restore IL-22 expression and promote full recovery from DSS-induced damage. These findings implicate the IL-36/IL-36R axis in the resolution of intestinal mucosal wounds.
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