Inhibition of Mitochondrial Translation Ameliorates Imiquimod-Induced Psoriasis-Like Skin Inflammation by Targeting Vγ4+ γδ T Cells

• DOI: 10.1016/j.jid.2023.09.275
• Publication Date: 2023-10-12T01:37:43Z
• Authors: Ayesha Dhillon-La...; Kathrin L. Braband; Eshraq Tantawy; Francesca Rampoldi; Yu-San Kao; Fatima Boukhallouk; Lis Noelia Velasquez; Panagiota Mamareli; Luana Silva; Luis Eduardo Alve...; Beate Weidenthale...; Luciana Berod; Luís Almeida; Tim Sparwasser

Psoriasis is an inflammatory skin disorder that is characterized by keratinocyte hyperproliferation in response to immune cell infiltration and cytokine secretion in the dermis. γδ T cells expressing the Vγ4 TCR chain are among the highest contributors of IL-17A, which is a major cytokine that drives a psoriasis flare, making Vγ4+ γδ T cells a suitable target to restrict psoriasis progression. In this study, we demonstrate that mitochondrial translation inhibition within Vγ4+ γδ T cells effectively reduced erythema, scaling, and skin thickening in a murine model of psoriatic disease. The antibiotic linezolid, which blocks mitochondrial translation, inhibited the production of mitochondrial-encoded protein cytochrome c oxidase in Vγ4+ γδ T cells and systemically reduced the frequencies of IL-17A+ Vγ4+ γδ T cells, effectively resolving IL-17A-dependent inflammation. Inhibiting mitochondrial translation could be a novel metabolic approach to interrupt IL-17A signaling in Vγ4+ T cells and reduce psoriasis-like skin pathophysiology.