Enrichement of type I interferon signalling in the colonic ILC2 under inflammatory condition

Abstract Background Group2 innate lymphoid cells (ILC2s) are known to contribute to a frontline defence against parasites and formation of allergic diseases, but little is known about the roles of ILC2s under intestinal inflammation including intestinal bowel diseases (IBD). In this study, we investigate the characteristics of ILC2s in health and colitis. Methods ILC2s were analysed in the mice with or without treatment of dextran sulphate sodium (DSS)-induced colitis, where surface markers and cytokine production was assessed by flow cytometry. The global gene expression of ILC2 in DSS-induced colitis and control mice were analysed by bulk RNA-sequencing (RNA-seq). Lastly, the mice was treated with anti-IFN-alpha/beta receptor1 (IFNAR1) antibody and then challenged to DSS-induced colitis. Results The number of ILC2s in the gastrointestinal tract was larger than that of spleen and liver in the healthy mice. At day 7 of DSS-induced colitis, IL-5 production from ILC2s was significantly reduced in flow cytometry data, and this was accompanied by enrichment of type I interferon (T1IFN) signalling in colitic ILC2 in RNA-seq data. Neutralisation of T1IFN signalling by anti-IFNAR antibody significantly increased severity of colitis. Conclusion Our data suggest that downregulation of Th2 cytokines and enrichment of T1IFN signatures in colitic ILC2s. T1IFN may stimulate ILC2 to induce colitis suppressive functions. This study was funded by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Transformative Research Areas(B): 21H05123; Advanced Research and Development Programs for Medical Innovation (AMED-CREST: 21gm1510002h0001, and 20gm1210001h0001; the Practical Research Project for Rare/Intractable Disease: 21ek0109556h0001)