美国国立癌症研究所Avinash Bhandoola小组发现，转录因子Tox2是肠道中ILC3的代谢适应和组织驻留所需。这一研究成果于2024年4月26日在线发表在国际学术期刊《免疫》上。

研究人员发现，Tox2对肠道第3组先天性淋巴细胞（ILC3）的维持和功能至关重要。肠道ILC3高度表达Tox2，而Tox2的耗竭则会显著减少肠道中的ILC3，但没有减少中心部位的ILC3，导致对鼠柠檬酸杆菌感染的控制缺陷。单细胞转录谱分析显示，Tox2缺失的肠道ILC3中己糖激酶2的表达量减少。

与糖酵解过程中对己糖激酶的需求相一致，Tox2^-/- ILC3利用糖酵解进行蛋白质翻译的能力也有所下降。异位表达己糖激酶2可挽救Tox2^-/-肠道ILC3的缺陷。缺氧和白细胞介素（IL）-17A可分别诱导ILC3中Tox2的表达，这表明了ILC3通过糖酵解代谢程序来适应波动环境的机制。这些研究结果揭示了胃肠道内ILC3的代谢适应需要Tox2的支持。

据悉，ILC3是肠道驻留ILC的主要亚群，在感染和组织修复中发挥着重要作用，但它们如何适应肠道环境以维持组织驻留尚不清楚。

附：英文原文

Title: Transcription factor Tox2 is required for metabolic adaptation and tissue residency of ILC3 in the gut

Author: Arundhoti Das, Gustavo Ulises Martinez-Ruiz, Nicolas Bouladoux, Apollo Stacy, Josquin Moraly, Maria Vega-Sendino, Yongge Zhao, Marieke Lavaert, Yi Ding, Abigail Morales-Sanchez, Christelle Harly, Mina O. Seedhom, Raj Chari, Parirokh Awasthi, Tomoko Ikeuchi, Yueqiang Wang, Jinfang Zhu, Niki M. Moutsopoulos, WanJun Chen, Jonathan W. Yewdell, Virginia Smith Shapiro, Sergio Ruiz, Naomi Taylor, Yasmine Belkaid, Avinash Bhandoola

Issue&Volume: 2024-04-26

Abstract: Group 3 innate lymphoid cells (ILC3) are the major subset of gut-resident ILC withessential roles in infections and tissue repair, but how they adapt to the gut environmentto maintain tissue residency is unclear. We report that Tox2 is critical for gut ILC3maintenance and function. Gut ILC3 highly expressed Tox2, and depletion of Tox2 markedly decreased ILC3 in gut but not at central sites, resultingin defective control of Citrobacter rodentium infection. Single-cell transcriptional profiling revealed decreased expression ofHexokinase-2 in Tox2-deficient gut ILC3. Consistent with the requirement for hexokinasesin glycolysis, Tox2/ ILC3 displayed decreased ability to utilize glycolysis for protein translation. Ectopicexpression of Hexokinase-2 rescued Tox2/ gut ILC3 defects. Hypoxia and interleukin (IL)-17A each induced Tox2 expression in ILC3, suggesting a mechanism by which ILC3 adjusts to fluctuating environmentsby programming glycolytic metabolism. Our results reveal the requirement for Tox2to support the metabolic adaptation of ILC3 within the gastrointestinal tract.

DOI: 10.1016/j.immuni.2024.04.001

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00206-1