Immunological Memory in Imiquimod-Induced Murine Model of Psoriasiform Dermatitis

Int J Mol Sci. 2020 Sep 30;21(19):7228. doi: 10.3390/ijms21197228.

Abstract

Psoriasis is a common chronic inflammatory skin condition manifested by T cell responses and characterized by preferential recurrence at previously inflamed sites upon withdrawal of treatment. The site-specific disease memory in psoriasis has been linked to CD8+CD103+ tissue-resident memory T cells (Trm) in the epidermis which were previously thought to only provide "frontline" protection against pathogens and immunosurveillance during cancer development. In this study, we correlated the presence of a subset of the Trm cells which are also CD49a+ with disease severity in human psoriatic lesions with acute and chronic disease. Using an imiquimod (IMQ)-induced murine model of psoriasiform dermatitis, we also investigated the level of CD49a+ Trm cells in acute, chronic and resolved psoriatic lesions. Investigation of clinical human samples showed that patient disease severity highly correlated with the numbers of epidermal CD49a+ Trm cells. Additionally, this subset of Trm cells was shown to persist in resolved lesions of murine psoriasiform dermatitis once clinical disease features had subsided. Importantly, these CD49a+ Trm cells showed significantly higher levels of granzyme B (GzmB) production compared to acute disease, suggesting a potential role of CD49a+ Trm cells for psoriatic re-occurrence in resolved patients. Better understanding of epidermal CD49a+ Trm cell activity is necessary for development of advanced treatment strategies for psoriasis to permit long-term, continuous disease control.

Keywords: psoriasis; resolved lesions; tissue-resident memory T cells.

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Disease Models, Animal
  • Epidermis / drug effects*
  • Epidermis / metabolism
  • Epidermis / pathology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Granzymes / genetics
  • Humans
  • Imiquimod / toxicity
  • Immunologic Memory / drug effects
  • Immunologic Memory / immunology*
  • Integrin alpha1 / immunology
  • Mice
  • Psoriasis / chemically induced
  • Psoriasis / immunology*
  • Psoriasis / pathology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • Integrin alpha1
  • Granzymes
  • Gzmb protein, mouse
  • Imiquimod