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

• Published in: Experimental Animals 2014, Vol.63(2), pp.235-246
• Main Authors: Akitsu, Aoi, Kakuta, Shigeru, Saijo, Shinobu, Iwakura, Yoichiro
• Format: Article
• Language: English
• Subjects: Colitis; IL-1; IL-17; innate lymphoid cells; Original; regulatory Tcells
• ISSN: 1341-1357; 1881-7122
• DOI: 10.1538/expanim.63.235

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.