PT  - JOURNAL ARTICLE
AU  - L Almeida
AU  - A Dhillon-LaBrooy
AU  - CN Castro
AU  - N Ayele
AU  - J Bartel
AU  - GM Carriche
AU  - M Guderian
AU  - S Lippens
AU  - S Dennerlein
AU  - C Hesse
AU  - BN Lambrecht
AU  - L Schauser
AU  - BR Blazar
AU  - M Kalesse
AU  - R Müller
AU  - LF Moita
AU  - T Sparwasser
TI  - Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis
AID  - 10.1101/832956
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 832956
4099  - http://biorxiv.org/content/early/2019/11/06/832956.short
4100  - http://biorxiv.org/content/early/2019/11/06/832956.full
AB  - 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 Th17 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 compromises the integrity of the electron transport chain (ETC). Ultimately, this leads to loss of mitochondrial metabolism and cytokine production in differentiating Th cells. In accordance, mice lacking Gfm1 in T cells are protected from EAE, demonstrating that this pathway plays a key role in maintaining T cell function and pathogenicity.