Cutting Edge: PD-1 Regulates Imiquimod-Induced Psoriasiform Dermatitis through Inhibition of IL-17A Expression by Innate γδ-Low T Cells. J Immunol 2015 Jul 15;195(2):421-5
Date
06/07/2015Pubmed ID
26048148Pubmed Central ID
PMC4490979DOI
10.4049/jimmunol.1500448Scopus ID
2-s2.0-84936805511 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
Programmed cell death 1 (PD-1) is a key regulatory molecule that has been targeted in human cancers, including melanoma. In clinical testing, Abs against PD-1 have resulted in psoriasiform dermatitis (PsD). To determine whether PD-1 regulates PsD, we compared skin responses of PD-1-deficient (PD-1KO) mice and wild-type (WT) controls in an imiquimod (IMQ)-induced murine model of psoriasis. PD-1KO mice showed severe epidermal hyperplasia, greater neutrophilic infiltration, and higher expression of Th17 cytokines (versus WT mice). IMQ exposure increased PD-1 expression by skin γδ-low (GDL) T cells and enhanced expression of PD-L1 by keratinocytes. Three-fold increases in the percentage of IL-17A(+) GDL T cells were observed in skin cell suspensions derived from IMQ-treated PD-1KO mice (versus WT controls), suggesting that the lack of PD-1 has a functional effect not only on αβ T cells, but also on GDL T cells, and that PD-1 may play a regulatory role in PsD.
Author List
Imai Y, Ayithan N, Wu X, Yuan Y, Wang L, Hwang STMESH terms used to index this publication - Major topics in bold
AminoquinolinesAnimals
Antibodies
Dermatitis
Disease Models, Animal
Gene Expression Regulation
Humans
Injections, Intraperitoneal
Interleukin-17
Keratinocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophil Infiltration
Neutrophils
Programmed Cell Death 1 Receptor
Receptors, Antigen, T-Cell, alpha-beta
Receptors, Antigen, T-Cell, gamma-delta
Signal Transduction
Th17 Cells
