AUTHOR=Irie Emi , Ishihara Rino , Mizushima Ichiro , Hatai Shunya , Hagihara Yuya , Takada Yoshiaki , Tsunoda Junya , Iwata Kentaro , Matsubara Yuta , Yoshimatsu Yusuke , Kiyohara Hiroki , Taniki Nobuhito , Sujino Tomohisa , Takabayashi Kaoru , Hosoe Naoki , Ogata Haruhiko , Teratani Toshiaki , Nakamoto Nobuhiro , Mikami Yohei , Kanai Takanori TITLE=Enrichment of type I interferon signaling in colonic group 2 innate lymphoid cells in experimental colitis JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.982827 DOI=10.3389/fimmu.2022.982827 ISSN=1664-3224 ABSTRACT=

Group 2 innate lymphoid cells (ILC2s) serve as frontline defenses against parasites. However, excluding helminth infections, it is poorly understood how ILC2s function in intestinal inflammation, including inflammatory bowel disease. Here, we analyzed the global gene expression of ILC2s in healthy and colitic conditions and revealed that type I interferon (T1IFN)-stimulated genes were up-regulated in ILC2s in dextran sodium sulfate (DSS)-induced colitis. The enhancement of T1IFN signaling in ILC2s in DSS-induced colitis was correlated with the downregulation of cytokine production by ILC2s, such as interleukin-5. Blocking T1IFN signaling during colitis resulted in exaggeration of colitis in both wild-type and Rag2-deficient mice. The exacerbation of colitis induced by neutralization of T1IFN signaling was accompanied by reduction of amphiregulin (AREG) in ILC2s and was partially rescued by exogenous AREG treatment. Collectively, these findings show the potential roles of T1IFN in ILC2s that contribute to colitis manifestation.