范德比尔特大学Jeffrey C. Rathmell团队研究出组织和CD4 T细胞亚群对氨基酸转运体SLC38A1的依赖性。2026年3月23日出版的《细胞—代谢》发表了这项成果。

该课题组研究人员通过体外和体内CRISPR筛选测试了CD4⁺ T细胞对AA的需求，并鉴定了对AA转运体SLC38A1 （SNAT1）的亚群和组织特异性依赖。虽然在肺炎症中T细胞在体内的持续和扩增是不可缺少的，但SLC38A1对Th1细胞驱动的实验性自身免疫性脑脊髓炎（EAE）至关重要，而不是Th17细胞驱动的，并有助于Th1细胞驱动的炎症性肠病。SLC38A1缺陷降低了Th1细胞中的mTORC1信号传导和糖酵解活性，部分原因是减少了谷氨酰胺摄取和破坏了己糖胺的生物合成和氧化还原调节。SLC38转运体的药理抑制也延迟了Th1介导的EAE，但对肺部炎症没有影响。CD4⁺ T细胞具有亚群和组织特异性的营养转运蛋白依赖性，这可能指导选择性免疫治疗的新代谢方法。

研究人员表示，氨基酸（AA）摄取对T细胞代谢和功能至关重要，但组织部位和炎症如何影响CD4⁺ T细胞亚群对特定AA的需求仍不确定。

附：英文原文

Title: Tissue and CD4 T cell subset dependence on the amino acid transporter SLC38A1

Author: Ayaka Sugiura, Katherine L. Beier, Channing Chi, Darren R. Heintzman, Xiang Ye, Melissa M. Wolf, Andrew R. Patterson, Jacqueline-Yvonne Cephus, Hanna S. Hong, Jeffrey M. Perera, Costas A. Lyssiotis, Dawn C. Newcomb, Jeffrey C. Rathmell

Issue&Volume: 2026-03-23

Abstract: Amino acid (AA) uptake is essential for T cell metabolism and function, but how tissue sites and inflammation affect CD4+ T cell subset requirements for specific AAs remains uncertain. Here, we tested CD4+ T cell AA demands with in vitro and in vivo CRISPR screens and identified subset- and tissue-specific dependencies on the AA transporter SLC38A1 (SNAT1). While dispensable for T cell persistence and expansion in vivo in lung inflammation, SLC38A1 was critical for Th1, but not Th17, cell-driven experimental autoimmune encephalomyelitis (EAE) and contributed to Th1 cell-driven inflammatory bowel disease. SLC38A1 deficiency reduced mTORC1 signaling and glycolytic activity in Th1 cells, in part by reducing glutamine uptake and disrupting hexosamine biosynthesis and redox regulation. Pharmacological inhibition of SLC38 transporters also delayed Th1-mediated EAE but did not affect lung inflammation. CD4+ T cells thus have subset- and tissue-specific nutrient transporter dependencies that may guide new metabolic approaches for selective immunotherapies.

DOI: 10.1016/j.cmet.2026.02.016

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(26)00085-9