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NKG2D Defines a Subset of Skin Effector Memory CD8 T Cells with Proinflammatory Functions in Vitiligo.
Journal of Investigative Dermatology ( IF 6.5 ) Pub Date : 2019-12-24 , DOI: 10.1016/j.jid.2019.11.013
Clément Jacquemin 1 , Christina Martins 1 , Fabienne Lucchese 1 , Denis Thiolat 1 , Alain Taieb 2 , Julien Seneschal 3 , Katia Boniface 4
Affiliation  

Vitiligo is an autoimmune disease that results from the loss of melanocytes, associated with skin infiltration of CD8+ effector memory T cells with a Tc1 skewed immune response. NKG2D is an activating receptor found on immune cells, in particular natural killer and activated CD8+ T cells, that are able to produce a high amount of IFN-γ. Here we found that NKG2D expression was increased in vitiligo skin CD8+ effector memory T cells and was promoted by IL-15. Phenotypic and functional analyses showed that NKG2D+ CD8+ skin effector memory T cells displayed an activated phenotype and produced elevated levels of both IFN-γ and tumor necrosis factor-α. Additional experiments revealed that vitiligo skin dendritic cells expressed the NKG2D ligands MICA-MICB, and in vitro experiments showed that these ligands could be induced on dendritic cells by IFN-α. Cultures of IFN-α-stimulated dendritic cells with skin NKG2D+ CD8+ T cells potentiated the production of type 1 cytokines, which was next inhibited by blocking the NKG2D/MICA-MICB interaction. These data show that NKG2D is a potential marker of pathogenic skin CD8+ effector memory T cells during vitiligo. Therefore, targeting NKG2D could be an attractive strategy in vitiligo, a disease for which there is a strong need of innovative treatments.

中文翻译:

NKG2D定义了白癜风中具有促炎功能的皮肤效应记忆CD8 T细胞的子集。

白癜风是一种自身免疫性疾病,是由黑素细胞的丢失导致的,它与具有Tc1偏向的免疫反应的CD8 +效应记忆T细胞的皮肤浸润有关。NKG2D是存在于免疫细胞上的活化受体,特别是天然杀伤细胞和活化的CD8 + T细胞,它们能够产生大量的IFN-γ。在这里,我们发现NKG2D在白癜风皮肤CD8 +效应记忆T细胞中表达增加,并由IL-15促进。表型和功能分析表明,NKG2D + CD8 +皮肤效应记忆T细胞表现出活化的表型,并产生升高水平的IFN-γ和肿瘤坏死因子-α。其他实验显示白癜风皮肤树突状细胞表达NKG2D配体MICA-MICB,体外实验表明,这些配体可被IFN-α诱导在树突状细胞上。IFN-α刺激的树突状细胞与皮肤NKG2D + CD8 + T细胞的培养可增强1型细胞因子的产生,然后通过阻断NKG2D / MICA-MICB相互作用来抑制1型细胞因子的产生。这些数据表明,NKG2D是白癜风期间致病性皮肤CD8 +效应记忆T细胞的潜在标志物。因此,靶向NKG2D可能是白癜风中的一种有吸引力的策略,这种疾病强烈需要创新的治疗方法。
更新日期:2019-12-24
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