Immunological Memory in Imiquimod-Induced Murine Model of Psoriasiform Dermatitis

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.

Transcutaneous Administration of Imiquimod Promotes T and B Cell Differentiation into Effector Cells or Plasma Cells

“…IMQ is also used to create psoriasis models, although it has already been clinically applied. When used as an adjuvant for vaccination, frequent administration is not expected, but it is also required to evaluate tissue-resident memory T cells from the viewpoint of safety evaluation [22]. In the future, based on the information obtained in this study, we aim to elucidate the mechanism underlying the transcutaneous adjuvant activity of IMQ, and we would like to proceed with studies of practical applications.…”

The Brain–Skin Axis in Psoriasis—Psychological, Psychiatric, Hormonal, and Dermatological Aspects

“…Physiological levels of glucocorticoids (GCs) enhance the immune response by increasing the response of T lymphocytes to IL-2, promote the synthesis of cytokines including IL-1 and IL-6, and increase biological sensitivity to other cytokines, such as granulocytic colony stimulating factor, granulocytic and macrophage colony-stimulating factor, and interferon γ (IFN-γ) [ 46 ]. Site-specific immunological memory response in psoriasis has been linked to both CD8+CD103+ tissue resident memory T cells (Trm) and dendritic cells in the epidermis [ 66 , 67 ]. Trm cells may rapidly induce an inflammation, triggering the recurrence of the disease [ 67 , 68 ].…”

Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

“…CD49a + T RM are involved in the pathogenesis of psoriasis. The number of epidermal CD8 + CD49a + T RM correlates with the severity of the disease [89], and an experimental blockade of CD49a in mice transplanted with psoriatic skin reduces the disease formation [76]. However, since the blockade of whole CD8 + T cells almost completely prevents disease development in the similar psoriatic skin-engrafted murine model [90], CD49a + T RM with IFN-γ production are not likely the key population for disease development, while the CD8 + T cell population likely includes a critical fraction for disease pathogenesis.…”