Excitatory amino acid transporter supports inflammatory macrophage responses

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外文摘要：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 signal-ing.EAAT2 is necessary for inflammatory macrophage polarization through sustaining mTORC1 activa-tion.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 mye-loid 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.

外文关键词：

MacrophagesExcitatory amino acid transporterGlutamateAspartatemTORC1

作者：

Zhending Gan、Yan Guo、Muyang Zhao、Yuyi Ye、Yuexia Liao、Bingnan Liu、Jie Yin、Xihong Zhou、Yuqi Yan、Yulong Yin、Wenkai Ren

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作者单位：

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

School of Nursing & School of Public Health,Yangzhou University,Yangzhou 225009,China

College of Animal Science and Technology,Hunan Agricultural University,Changsha 410128,China

Institute of Subtropical Agriculture,Chinese Academy of Sciences,Changsha,410125,China

Department of Veterinary Medicine,College of Animal Sciences,Zhejiang University,Hangzhou 310058,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaLaboratory of Lingnan Modern Agriculture ProjectNational Center of Technology Innovation for Pigsdouble firstclass discipline promotion project

项目编号：

32225047U22A20510NT2021005NCTIP-XD/B132023B10564001

出版年：

2024

DOI：

10.1016/j.scib.2024.03.055

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

年,卷(期)：2024.69(15)