This repository contains code used for: Yang Zang, Shaorui Liu, Zebing Rao, Yinsheng Wang, Boya Zhang, Hui Li, Yingjiao Cao, Jie Zhou, Zhuxia Shen, Shengzhong Duan, Danyang He, Heping Xu, Retinoid X receptor gamma dictates the activation threshold of group 2 innate lymphoid cells and limits type 2 inflammation in the small intestine, Immunity, 2023, ISSN 1074-7613, doi.org/10.1016/j.immuni.2023.08.019.
Summary: Group 2 innate lymphoid cells (ILC2s) are crucial in promoting type 2 inflammation that contributes to both anti-parasite immunity and allergic diseases. However, the molecular checkpoints in ILC2s that determine whether to immediately launch a proinflammatory response are unknown. Here, we found that retinoid X receptor gamma (Rxrg) was highly expressed in small intestinal ILC2s and rapidly suppressed by alarmin cytokines. Genetic deletion of Rxrg did not impact ILC2 development but facilitated ILC2 responses and the tissue inflammation induced by alarmins. Mechanistically, RXRγ maintained the expression of its target genes that support intracellular cholesterol efflux, which in turn reduce ILC2 proliferation. Furthermore, RXRγ expression prevented ILC2 response to mild stimulations, including low doses of alarmin cytokine and mechanical skin injury. Together, we propose that RXRγ expression and its mediated lipid metabolic states function as a cell-intrinsic checkpoint that confers the threshold of ILC2 activation in the small intestine. Keywords: type 2 inflammation; allergy; small intestine; group 2 innate lymphoid cells; retinoid X receptor gamma; activation threshold; lipid homeostasis; CUT&Tag; RNA-seq
Link to paper: https://www.cell.com/immunity/fulltext/S1074-7613(23)00375-8
Any questions about the data, please directly contact Dr. Heping Xu: xuheping@westlake.edu.cn