Reinforcing involvement of NK cells in psoriasiform dermatitis animal model.

Abstract

Psoriasis (Ps) is a chronic inflammatory immune-mediated disease with skin and joint manifestations, characterized by abnormal and rapid proliferation of keratinocytes and infiltration of psoriatic lesions with immune cells. Extensive literature suggests that Ps is a T-cell mediated disease its pathogenesis being highly related to innate and adaptative immune cells. Although natural killer (NK) cells are involved in the inflammatory process of Ps through pro-inflammatory cytokine secretion (tumor necrosis factor α, interferon γ), their role in this pathology is not yet fully elucidated. In order to study the involvement of NK subpopulations in the pathogenesis of Ps we used the imiquimod-based mouse model of psoriasiform dermatitis and NK cells complex phenotype patterns from peripheral blood (PB) and spleen were investigated. Skin inflammation and the disease severity were assessed using in vivo measurements (erythema, desquamation and induration parameters, PASI modified score), splenomegaly assessment and histopathological evaluation. Phenotypic characterization of NK cells in imiquimod (IMQ)-treated mice was performed by flow cytometry, for both PB and spleen cell suspension. A large panel of surface markers was used: maturation and activation markers [cluster of differentiation (CD)49b, CD11b, CD43, CD27, KLRG1, CD335, CD69, CD28, gp49R, CD45R, CD11c] and markers for cytokine receptors (CD25, CD122, CD132). Our experimental data showed important differences in IMQ-treated mouse NK cell phenotype as compared to control group. The maturation markers (CD11b, CD43, CD27, KLRG1) were found increased on NK cells, in periphery and spleen, while CD49b+NK1.1+ was significantly lower, and the alterations correlated with the severity of the disease. Our findings reflect the immune engagement toward activatory profile of NK cells and draw attention to evaluating Ps intensity correlated with the mature profile of circulating NK cells.