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伪饥饿信号揭示SLC7A11是Treg细胞增殖潜能的关键决定因素
作者:小柯机器人 发布时间:2021/5/20 14:09:46

意大利内分泌生物学研究所Giuseppe Matarese和IRCCS多媒体Paola de Candia研究组合作取得最新进展。他们发现伪饥饿信号揭示氨基酸转运蛋白SLC7A11作为控制调节性T(Treg)细胞增殖潜能的关键决定因素。相关论文发表在2021年5月17日出版的《免疫学》杂志上。

他们报告伪饥饿信号通过整合的转录反应逆转了人类Treg细胞的体外无能,涉及到增殖、代谢和跨膜溶质载体的运输。在分子水平上,Treg细胞的增殖反应取决于胱氨酸/谷氨酸反转运蛋白溶质载体(SLC)7A11的诱导,该载体的表达受核因子红系2相关因子2(NRF2)控制。患有复发缓解型多发性硬化症(RRMS)的受试者的Treg细胞中的SLC7A11诱导受损,这是一种与Treg细胞增殖能力降低有关的自身免疫性疾病。用富马酸二甲酯(DMF)治疗RRMS受试者可挽救SLC7A11诱导并完全恢复Treg细胞扩增。

这些结果表明,以前无法识别的机制可能解释了自身免疫中Treg细胞的进行性丧失,并揭示了SLC7A11作为挽救Treg细胞增殖的主要靶标。

据介绍,人CD4 + CD25hiFOXP3 + Treg细胞是控制免疫自耐受性和体内平衡的关键因素。

附:英文原文

Title: Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential

Author: Claudio Procaccini, Silvia Garavelli, Fortunata Carbone, Dario Di Silvestre, Claudia La Rocca, Dario Greco, Alessandra Colamatteo, Maria Teresa Lepore, Claudia Russo, Giusy De Rosa, Deriggio Faicchia, Francesco Prattichizzo, Sarah Grossi, Paola Campomenosi, Fabio Buttari, Pierluigi Mauri, Antonio Uccelli, Marco Salvetti, Vincenzo Brescia Morra, Danila Vella, Mario Galgani, Maria Mottola, Bruno Zuccarelli, Roberta Lanzillo, Giorgia Teresa Maniscalco, Diego Centonze, Paola de Candia, Giuseppe Matarese

Issue&Volume: 2021-05-17

Abstract: Human CD4+CD25hiFOXP3+ regulatory T (Treg) cells are key players in the control of immunological self-toleranceand homeostasis. Here, we report that signals of pseudo-starvation reversed humanTreg cell in vitro anergy through an integrated transcriptional response, pertaining to proliferation,metabolism, and transmembrane solute carrier transport. At the molecular level, theTreg cell proliferative response was dependent on the induction of the cystine/glutamateantiporter solute carrier (SLC)7A11, whose expression was controlled by the nuclearfactor erythroid 2-related factor 2 (NRF2). SLC7A11 induction in Treg cells was impairedin subjects with relapsing-remitting multiple sclerosis (RRMS), an autoimmune disorderassociated with reduced Treg cell proliferative capacity. Treatment of RRMS subjectswith dimethyl fumarate (DMF) rescued SLC7A11 induction and fully recovered Treg cellexpansion. These results suggest a previously unrecognized mechanism that may accountfor the progressive loss of Treg cells in autoimmunity and unveil SLC7A11 as majortarget for the rescue of Treg cell proliferation.

DOI: 10.1016/j.immuni.2021.04.014

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00176-X

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