氨基酸通过小G蛋白Rag和Rheb促进激酶mTORC1活性和



本期文章:《免疫》:Volume 51 Issue 6

美国圣裘德儿童研究医院迟洪波课题组的一项最新研究发现,氨基酸通过小G蛋白Rag和Rheb促进激酶mTORC1活性和Treg细胞功能。该项研究成果发表在2019年12月17日出版的《免疫》上。

研究人员证明了氨基酸通过引发和维持TCR诱导的mTORC1活性来维持Treg细胞功能。氨基酸(尤其是精氨酸和亮氨酸)诱导了mTORC1的激活,并伴随着mTOR和Tsc复合物的动态溶酶体定位。Rag和Rheb GTPases是效应Treg(eTreg)细胞中氨基酸依赖性mTORC1激活的中央调节因子。携带RagA-RagB-或Rheb1-Rheb2缺陷型Treg细胞的小鼠发展成致命的自身免疫疾病,并降低了eTreg细胞的积累和功能。RagA-RagB调节线粒体和溶酶体的适应性,而Rheb1-Rheb2强制eTreg细胞抑制性基因特征。总之,这些发现揭示了氨基酸信号转导对促进和维持mTORC1激活以及Treg细胞功能性编程的关键需求。

据介绍,Treg细胞是免疫耐受的关键介导者,其活性取决于T细胞受体(TCR)和mTORC1激酶信号传导,但尚不清楚对决定这些途径功能激活的机制的了解。

附:英文原文

Title: Amino Acids License Kinase mTORC1 Activity and Treg Cell Function via Small G Proteins Rag and Rheb

Author: Hao Shi, Nicole M. Chapman, Jing Wen, Cliff Guy, Lingyun Long, Yogesh Dhungana, Sherri Rankin, Stephane Pelletier, Peter Vogel, Hong Wang, Junmin Peng, Kun-Liang Guan, Hongbo Chi

Issue&Volume: 2019/12/17

Abstract: Regulatory T (Treg) cells are critical mediators of immune tolerance whose activitydepends upon T cell receptor (TCR) and mTORC1 kinase signaling, but the mechanismsthat dictate functional activation of these pathways are incompletely understood.Here, we showed that amino acids license Treg cell function by priming and sustainingTCR-induced mTORC1 activity. mTORC1 activation was induced by amino acids, especiallyarginine and leucine, accompanied by the dynamic lysosomal localization of the mTORand Tsc complexes. Rag and Rheb GTPases were central regulators of amino acid-dependentmTORC1 activation in effector Treg (eTreg) cells. Mice bearing RagA-RagB- or Rheb1-Rheb2-deficientTreg cells developed a fatal autoimmune disease and had reduced eTreg cell accumulationand function. RagA-RagB regulated mitochondrial and lysosomal fitness, while Rheb1-Rheb2enforced eTreg cell suppressive gene signature. Together, these findings reveal acrucial requirement of amino acid signaling for licensing and sustaining mTORC1 activationand functional programming of Treg cells.

DOI: 10.1016/j.immuni.2019.10.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30418-2

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx




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