Vitiligo Skin T Cells Are Prone to Produce Type 1 and Type 2 Cytokines to Induce Melanocyte Dysfunction and Epidermal Inflammatory Response Through Jak Signaling
Vitiligo Skin T Cells Are Prone to Produce Type 1 and Type 2 Cytokines to Induce Melanocyte Dysfunction and Epidermal Inflammatory Response Through Jak Signaling
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DOI：
10.1016/j.jid.2021.09.015
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发表时间：
2022-03-21
影响因子：
6.5
通讯作者：
Boniface, Katia
中科院分区：
文献类型：
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作者：
Martins, Christina;Migayron, Laure;Boniface, Katia
白癜风是一种T细胞介导的炎症性皮肤病，其特征是表皮黑素细胞的丢失。然而，黑素细胞对T细胞微环境的反应对疾病的病理生理学的贡献仍不清楚。在这里，使用NanoString技术和多重ELISA，我们表明，活动性白癜风皮损周围皮肤的特点是突出的1型和2型相关的免疫反应。白癜风皮肤T细胞分泌组下调黑素细胞功能和粘附，同时增加黑素细胞线粒体代谢和表皮细胞表达炎性细胞因子和趋化因子。Jak 1/2抑制剂ruxolitinib强烈抑制了对表皮细胞的这种作用。我们的数据强调白癜风比以前认为的更复杂，具有显著的辅助性T细胞1 e型和辅助性T细胞2 e型相关细胞因子诱导表皮细胞炎症反应的联合活性。黑素细胞似乎不仅是白癜风中T细胞的靶点，而且可能积极促进炎症的持续。Jak抑制剂可以防止T细胞对表皮细胞和色素沉着的影响，突出了它们在白癜风中的潜在临床益处。
Vitiligo is a T cellemediated inflammatory skin disorder characterized by the loss of epidermal melanocytes. However, the contribution of melanocytes to the physiopathology of the disease in response to the T-cell microenvironment remains unclear. Here, using NanoString technology and multiplex ELISA, we show that active vitiligo perilesional skin is characterized by prominent type 1 and 2 associated immune responses. The vitiligo skin T-cell secretome downregulated melanocyte function and adhesion while increasing melanocyte mitochondrial metabolism and expression of inflammatory cytokines and chemokines by epidermal cells. The Jak1/2 inhibitor ruxolitinib strongly inhibited such effects on epidermal cells. Our data highlight that vitiligo is more complex than previously thought, with prominent combined activities of both T helper type 1e and T helper type 2erelated cytokines inducing inflammatory responses of epidermal cells. Melanocytes do not appear only to be a target of T cells in vitiligo but could actively contribute to perpetuate inflammation. Jak inhibitors could prevent the impact of T cells on epidermal cells and pigmentation, highlighting their potential clinical benefit in vitiligo.