Rag2-deficient IL-1 receptor antagonist-deficient mice are a novel colitis model in which innate lymphoid cell-derived IL-17 is involved in the pathogenesis

Abstract

Il1rn-/- mice spontaneously develop arthritis and aortitis by an autoimmune mechanism and also develop dermatitis by an autoinflammatory mechanism. Here, we show that Rag2-/-Il1rn-/- mice develop spontaneous colitis with high mortality, making a contrast to the suppression of arthritis in these mice. Enhanced IL-17A expression in group 3 innate lymphoid cells (ILC3s) was observed in the colon of Rag2-/-Il1rn-/- mice. IL-17A-deficiency prolonged the survival of Rag2-/-Il1rn-/- mice, suggesting a pathogenic role of this cytokine in the development of intestinal inflammation. Although IL-17A-producing T cells were increased in Il1rn-/- mice, these mice did not develop colitis, because CD4+Foxp3+ regulatory T cell population was also expanded. Thus, excess IL-1 signaling and IL-1-induced IL-17A from ILC3s cause colitis in Rag2-/-Il1rn-/- mice in which Treg cells are absent. These observations suggest that the balance between IL-17A-producing cells and Treg cells is important to keep the immune homeostasis of the colon. © 2014 Japanese Association for Laboratory Animal Science.