Institute of Medical Microbiology and Hygiene, University Medical Center of the Johannes University Gutenberg, Mainz, Germany.
Institute of Medical Microbiology and Hygiene, University Medical Center of the Johannes University Gutenberg, Mainz, Germany; Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, São Paulo, Brazil.
J Invest Dermatol. 2024 Apr;144(4):844-854.e2. doi: 10.1016/j.jid.2023.09.275. Epub 2023 Oct 12.
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.
银屑病是一种炎症性皮肤疾病，其特征是角质形成细胞在真皮中免疫细胞浸润和细胞因子分泌的刺激下过度增殖。表达 Vγ4 TCR 链的 γδ T 细胞是 IL-17A 的主要贡献者之一，IL-17A 是驱动银屑病发作的主要细胞因子，这使得 Vγ4 γδ T 细胞成为限制银屑病进展的合适靶点。在这项研究中，我们证明了 Vγ4 γδ T 细胞内的线粒体翻译抑制可有效减轻银屑病疾病小鼠模型中的红斑、鳞屑和皮肤增厚。抗生素利奈唑胺可阻断线粒体翻译，抑制 Vγ4 γδ T 细胞中线粒体编码蛋白细胞色素 c 氧化酶的产生，并在系统水平上降低 IL-17A Vγ4 γδ T 细胞的频率，从而有效缓解 IL-17A 依赖性炎症。抑制线粒体翻译可能是一种新的代谢方法，可阻断 Vγ4 T 细胞中的 IL-17A 信号传导并减轻银屑病样皮肤病理生理学。
