title: Cutting Edge: PD-1 Regulates Imiquimod-Induced Psoriasiform Dermatitis through Inhibition of IL-17A Expression by Innate γδ-Low T Cells.
abstract: 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.
authors.affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226; and.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Imai
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Ayithan
authors.affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226; and.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226 sthwang@mcw.edu lilywang@mcw.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226; and sthwang@mcw.edu lilywang@mcw.edu.
authors.forename: Sam T
authors.initials: ST
authors.lastname: Hwang
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003872:Dermatitis / Q000151:congenital* / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D000077271:Imiquimod; D007274:Injections, Intraperitoneal; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D015603:Keratinocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000634:Aminoquinolines; D000906:Antibodies; C508717:IL17A protein, human; D020381:Interleukin-17; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077271:Imiquimod