Excitatory amino acid transporter supports inflammatory macrophageresponses  

兴奋性氨基酸转运载体支持促炎巨噬细胞极化

作　　者：Zhending Gan Yan Guo Muyang Zhao Yuyi Ye Yuexia Liao Bingnan Liu Jie Yin Xihong Zhou Yuqi Yan Yulong Yin Wenkai Ren 甘振丁;郭艳;赵沐阳;叶钰怡;廖月霞;刘炳南;尹杰;周锡红;严玉祺;印遇龙;任文凯

机构地区：[1]State Key Laboratory of Swine and Poultry Breeding Industry,Guangdong Laboratory of Lingnan Modern Agriculture,College of Animal Science,South China Agricultural University,Guangzhou 510642,China [2]School of Nursing&School of Public Health,Yangzhou University,Yangzhou 225009,China [3]College of Animal Science and Technology,Hunan Agricultural University,Changsha 410128,China [4]Institute of Subtropical Agriculture,Chinese Academy of Sciences,Changsha 410125,China [5]Department of Veterinary Medicine,College of Animal Sciences,Zhejiang University,Hangzhou 310058,China

出　　处：《Science Bulletin》2024年第15期2405-2419,共15页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (32225047 and U22A20510);Laboratory of Lingnan Modern Agriculture Project (NT2021005);National Center of Technology Innovation for Pigs (NCTIP-XD/B13);double first-class discipline promotion project (2023B10564001)。

摘　　要：Excitatory amino acid transporters(EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues.However, the subcellular location and function of EAAT2 in macrophages are still obscure. In this study,we demonstrated that LPS stimulation increases expression of EAAT2(coded by Slc1a2) via NF-κB signaling. EAAT2 is necessary for inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal EAAT2 mediates lysosomal glutamate and aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis and mTORC1. We also found that mice with myeloid depletion of Slc1a2 show alleviated inflammatory responses in LPS-induced systemic inflammation and high-fat diet induced obesity. Notably, patients with type Ⅱ diabetes(T2D) have a higher level of expression of lysosomal EAAT2 and activation of mTORC1 in blood macrophages. Taken together, our study links the subcellular location of amino acid transporters with the fate decision of immune cells,which provides potential therapeutic targets for the treatment of inflammatory diseases.

关 键 词：MACROPHAGES Excitatory amino acid transporter GLUTAMATE ASPARTATE mTORC1 

分 类 号：R392[医药卫生—免疫学]