Biological depletion of neutrophils attenuates pro-inflammatory markers and the development of the psoriatic phenotype in a murine model of psoriasis

Clin Immunol. 2020 Jan:210:108294. doi: 10.1016/j.clim.2019.108294. Epub 2019 Oct 31.

Abstract

Although neutrophils are considered a histologic hallmark of psoriasis, their pathophysiologic role in psoriasis remains unclear. We characterized the effects of neutrophil depletion via injection of monoclonal antibody 1A8 on the development of imiquimod (IMQ)-induced psoriatic lesions in a murine model. Lesions were followed with photographs and histologic analysis, revealing reduced psoriasiform scale and epidermal hyperplasia in neutrophil-depleted. ELISA and flow cytometry were used to determine relative levels of cytokines and immune cells. Compared to controls, IMQ-treated neutropenic mice had significantly lower levels of macrophages in tissue samples (P < .05) and displayed significantly lower numbers of CD4+ T-cells (P < .05). Neutropenic animals exhibited lower levels of TNF-α, IFN-γ, and IL-1β than controls (P < .05). These results show that neutropenia reduces the development of psoriasiform skin lesions and substantially decreases infiltration of pro-inflammatory cytokines and immune cells to IMQ-induced cutaneous lesions, suggesting an active role of neutrophils in maintaining inflammation in psoriasis.

Keywords: Cytokines; Imiquimod; Inflammation; Macrophages; Neutrophils; Psoriasis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Imiquimod
  • Inflammation / immunology*
  • Leukocyte Reduction Procedures
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology*
  • Phenotype
  • Psoriasis / immunology*

Substances

  • Biomarkers
  • Cytokines
  • Imiquimod