P0013The protective roles of Group 2 innate lymphoid cells in acute intestinal inflammation

Abstract Background IL-5 is known to be produced by Type 2 immune cells, namely Group 2 innate lymphoid cells (ILC2s) and T helper 2 (TH2) cells and to enhance the accumulation of eosinophils in the intestine. However, it is poorly understood how IL-5 functions under intestinal inflammation, including inflammatory bowel diseases (IBDs). The aim of this study is to elucidate the role of IL-5 and ILC2 in murine experimental colitis. Methods Immune cell populations in the colonic lamina propria were profiled by single cell RNA-sequencing (scRNA-seq). Three lines of transgenic mice, (1) IL-5red (IL-5 KO) mice, (2) IL-5red x DTA (ILC2 KO) mice and (3) IL-5red x Ifnar1-flox (Ifnar1-cKOΔILC2) mice, were subjected to 2.5% dextran sulfate sodium (DSS) to induce colitis. Then, the body weight and colon length in the mice with DSS-induced colitis were examined, and compared with wild-type (WT) mice. Results ILC2 population was abundant in the colonic lamina propria and expressed type 2 cytokines, such as Il5 and Il13, as well as tissue repair factor Areg encoding amphiregulin. The weight reduction was significantly greater in IL-5 KO mice, ILC2 KO mice and Ifnar1-cKOΔILC2 mice compared to WT mice. The colon length was shorter in IL-5 KO mice, ILC2 KO mice and Ifnar1-cKOΔILC2 mice. The histological severity was greater in IL-5 KO mice, ILC2 KO mice and Ifnar1-cKOΔILC2 mice than in WT mice. Collectively, these differences indicate that the condition of colitis was more exacerbated in IL-5 KO mice, ILC2 KO mice and Ifnar1-cKOΔILC2 mice. Conclusion This study suggests potential anti-inflammatory effects of IL-5 and ILC2 in colitis. Enhancement of tissue protective functions of ILC2 may offer novel therapeutic approaches for treating intestinal inflammation. Conflict of interest: Ms. Tajima, Lili: No conflict of interest Irie, Emi: No conflict of interest Mizushima, Ichiro: No conflict of interest Kan, Ka: No conflict of interest Kaieda, Yuta: No conflict of interest Tsunoda, Junya: No conflict of interest Mikami, Yohei: No conflict of interest Kanai, Takanori: No conflict of interest