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.

虽然抗生素旨在专门针对细菌，但大多数已知会影响宿主细胞生理。此外，由于尚不清楚的原因，一些抗生素类别被报告为具有免疫抑制作用。在这里，我们展示了利奈唑胺，一种核糖体靶向抗生素 (RAbo)，有效地阻止了 T 细胞介导的自身免疫性疾病的进程。利奈唑胺和其他 RAbos 是体外T helper-17 细胞效应功能的强抑制剂，表明这种效果与其抗生素活性无关。在分化的 T 细胞中扰乱线粒体翻译，无论是使用 RAbos 还是通过抑制线粒体延伸因子 G1 (mEF-G1) 都会逐渐损害电子传递链的完整性。最终，这导致氧化磷酸化不足，降低烟酰胺腺嘌呤二核苷酸浓度并削弱分化 T 细胞中细胞因子的产生。因此，T 细胞中缺乏 mEF-G1 的小鼠可以免受实验性自身免疫性脑脊髓炎的影响，这表明该途径对于维持 T 细胞功能和致病性至关重要。