Prostaglandin E2controls the metabolic adaptation of T cells to the intestinal microenvironment

Author:

Villa Matteo,Sanin David E.,Apostolova Petya,Corrado Mauro,Kabat Agnieszka M.,Cristinzio Carmine,Regina Annamaria,Carrizo Gustavo E.,Rana Nisha,Stanczak Michal A.,Baixauli Francesc,Grzes Katarzyna M.,Cupovic Jovana,Solagna Francesca,Hackl Alexandra,Globig Anna-Maria,Hässler Fabian,Puleston Daniel J.,Kelly Beth,Cabezas-Wallscheid Nina,Hasselblatt Peter,Bengsch Bertram,Zeiser Robert,Sagar ,Buescher Joerg M.,Pearce Edward J,Pearce Erika L.

Abstract

AbstractImmune cells must adapt to different environments during the course of an immune response. We studied the adaptation of CD8+T cells to the intestinal microenvironment and how this process shapes their residency in the gut. CD8+T cells progressively remodel their transcriptome and surface phenotype as they acquire gut residency, and downregulate expression of mitochondrial genes. Human and mouse gut-resident CD8+T cells have reduced mitochondrial mass, but maintain a viable energy balance to sustain their function. We found that the intestinal microenvironment is rich in prostaglandin E2(PGE2), which drives mitochondrial depolarization in CD8+T cells. Consequently, these cells engage autophagy to clear depolarized mitochondria, and enhance glutathione synthesis to scavenge reactive oxygen species (ROS) that result from mitochondrial depolarization. Impairing PGE2sensing promotes CD8+T cell accumulation in the gut, while tampering with autophagy and glutathione negatively impacts the T cell population. Thus, a PGE2-autophagy-glutathione axis defines the metabolic adaptation of CD8+T cells to the intestinal microenvironment, to ultimately influence the T cell pool.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3