Journal
CLINICAL IMMUNOLOGY
Volume 181, Issue -, Pages 51-59Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2017.06.002
Keywords
Psoriasis; Programmed death-1; PD-1; Double negative T cells; IFN-gamma; Effector memory T cells
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Funding
- intramural MeDDrive program, University of Technology Dresden [60.364]
- Fritz-Thyssen-Foundation [10.15.1.019MN]
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The autoimmune/inflammatory disorder psoriasis is characterized by keratinocyte proliferation and immune cell infiltration of the skin. TCR+ CD3(+) CD4(-) CDS- 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-gamma, 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. (C) 2017 Elsevier Inc. All rights reserved.
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