Brandt D, Sergon M, Abraham S, Mäbert K, Hedrich C M
Division of Pediatric Rheumatology and Immunology, Children's Hospital Dresden, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
Institute of Pathology, Faculty of Medicine Carl Gustav Carus, TU Dresden, Dresden, Germany.
Clin Immunol. 2017 Aug;181:51-59. doi: 10.1016/j.clim.2017.06.002. Epub 2017 Jun 15.
The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCRCD3CD4CD8 "double negative" (DN) T cells can derive from CD8 T cells through the down-regulation of CD8. The inhibitory molecule programmed death (PD-)1 is expressed on activated T cells and plays a role in the maintenance of peripheral tolerance. A subset of DN T cells, characterized by the expression of PD-1, has recently been demonstrated to be self-reactive. We demonstrate that a majority of DN T cells exhibits effector memory phenotypes, express IFN-γ, and fail to proliferate. DN T cells from psoriasis patients are characterized by reduced DNA methylation of the IFNG gene and increased PD-1 expression. Furthermore, PD-1 positive DN T cells infiltrate the epidermis in psoriatic skin lesions. Our observations offer additional insight into the molecular pathophysiology of plaque psoriasis and show promise as potential disease biomarkers and/or therapeutic targets for future interventions.
自身免疫性/炎症性疾病银屑病的特征是角质形成细胞增殖和皮肤免疫细胞浸润。TCRCD3CD4CD8“双阴性”（DN）T细胞可通过CD8的下调从CD8 T细胞衍生而来。抑制性分子程序性死亡（PD-）1在活化的T细胞上表达，并在维持外周耐受中发挥作用。最近已证明，以PD-1表达为特征的DN T细胞亚群具有自身反应性。我们证明，大多数DN T细胞表现出效应记忆表型，表达IFN-γ，并且无法增殖。银屑病患者的DN T细胞的特征是IFNG基因的DNA甲基化减少和PD-1表达增加。此外，PD-1阳性DN T细胞浸润银屑病皮肤病变的表皮。我们的观察结果为斑块状银屑病的分子病理生理学提供了更多见解，并有望作为未来干预的潜在疾病生物标志物和/或治疗靶点。
