德国汉诺威医学院和亥姆霍兹感染研究中心Tim Sparwasser课题组发现,靶向核糖体的抗生素通过阻断线粒体蛋白合成来损害T细胞效应子功能并改善自身免疫性。相关论文于2020年11月24日在线发表在《免疫》杂志上。
Title: Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis
Author: Luís Almeida, Ayesha Dhillon-LaBrooy, Carla N. Castro, Nigatu Adossa, Guilhermina M. Carriche, Melanie Guderian, Saskia Lippens, Sven Dennerlein, Christina Hesse, Bart N. Lambrecht, Luciana Berod, Leif Schauser, Bruce R. Blazar, Markus Kalesse, Rolf Müller, Luís F. Moita, Tim Sparwasser
Issue&Volume: 2020-11-24
Abstract: While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressively compromised the integrity of the electron transport chain. Ultimately, this led to deficient oxidative phosphorylation, diminishing nicotinamide adenine dinucleotide concentrations and impairing cytokine production in differentiating T cells. In accordance, mice lacking mEF-G1 in T cells were protected from experimental autoimmune encephalomyelitis, demonstrating that this pathway is crucial in maintaining T cell function and pathogenicity.
DOI: 10.1016/j.immuni.2020.11.001
Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30466-0
Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:43.474
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx
本期文章:《免疫》:Online/在线发表