西湖大学Heping Xu研究小组近日取得一项新成果。经过不懈努力，他们的发现类维生素A族X受体γ决定了2型先天淋巴细胞（ILC2）的活化阈值并抑制小肠中2型炎症的发生。这一研究成果发表在2023年9月14日出版的国际学术期刊《免疫》上。

研究人员发现类视黄醇X受体γ（Rxrg）在小肠ILC2中高表达，并被alarmin细胞因子迅速抑制。Rxrg基因缺失并不影响ILC2的发育，但会促进ILC2反应和警报蛋白诱导的组织炎症。在机制上，RXRγ维持其支持细胞内胆固醇外排的靶基因表达，从而减少ILC2增殖。

此外，RXRγ表达阻止了ILC2对轻度刺激的反应，包括低剂量警报细胞因子和机械性皮肤损伤。总之，该研究发现RXRγ表达及其介导的脂质代谢状态是细胞内在的检查点，赋予小肠ILC2激活的阈值。

据介绍，2型先天淋巴细胞对于2型炎症的调控至关重要，2型炎症参与抗寄生虫免疫和过敏性疾病。然而，尚不清楚影响ILC2是否立即启动促炎反应的分子检查点。

附：英文原文

Title: Retinoid X receptor gamma dictates the activation threshold of group 2 innate lymphoid cells and limits type 2 inflammation in the small intestine

Author: Yang Zang, Shaorui Liu, Zebing Rao, Yinsheng Wang, Boya Zhang, Hui Li, Yingjiao Cao, Jie Zhou, Zhuxia Shen, Shengzhong Duan, Danyang He, Heping Xu

Issue&Volume:

Abstract: Group 2 innate lymphoid cells (ILC2s) are crucial in promoting type 2 inflammationthat contributes to both anti-parasite immunity and allergic diseases. However, themolecular checkpoints in ILC2s that determine whether to immediately launch a proinflammatoryresponse are unknown. Here, we found that retinoid X receptor gamma (Rxrg) was highly expressed in small intestinal ILC2s and rapidly suppressed by alarmincytokines. Genetic deletion of Rxrg did not impact ILC2 development but facilitated ILC2 responses and the tissue inflammationinduced by alarmins. Mechanistically, RXRγ maintained the expression of its targetgenes that support intracellular cholesterol efflux, which in turn reduce ILC2 proliferation.Furthermore, RXRγ expression prevented ILC2 response to mild stimulations, includinglow doses of alarmin cytokine and mechanical skin injury. Together, we propose thatRXRγ expression and its mediated lipid metabolic states function as a cell-intrinsiccheckpoint that confers the threshold of ILC2 activation in the small intestine.

DOI: 10.1016/j.immuni.2023.08.019

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00375-8