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. doi: 10.4049/jimmunol.1500448. Epub 2015 Jun 5.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aminoquinolines / administration & dosage
  • Animals
  • Antibodies / pharmacology
  • Dermatitis / congenital*
  • Dermatitis / etiology
  • Dermatitis / genetics
  • Dermatitis / immunology
  • Dermatitis / pathology
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Imiquimod
  • Injections, Intraperitoneal
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Keratinocytes / immunology
  • Keratinocytes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Infiltration
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Signal Transduction
  • Th17 Cells / immunology*
  • Th17 Cells / pathology

Substances

  • Aminoquinolines
  • Antibodies
  • IL17A protein, human
  • Interleukin-17
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Imiquimod

Supplementary concepts

  • Seborrhea-Like Dermatitis with Psoriasiform Elements