Phenotypic changes of lymphocyte populations in psoriasiform dermatitis animal model

Abstract

Psoriasis is a T cell mediated, chronic inflammatory autoimmune skin disease that affects up to 2–3% of the global population and leads to a decrease in quality of life. Experimental data accumulated in recent years highlighted the important role played by the immune system in the pathogenesis of this disease. Non-human psoriasis models are an important research tool that attempts to reproduce the clinical features of the disease in order to explain the pathogenesis of psoriasis and to identify possible therapeutic targets. Imiquimod-based murine model of psoriatic dermatitis is an alternative to traditional models of experimental psoriasis in mice and the induced dermatitis closely mimics the pathologic changes in human psoriasis. In order to emphasize changes in immune cell populations involved in lesion pathogenesis, we performed a murine model of psoriasiform dermatitis model by topical IMQ application. The progress and the severity of IMQ-induced skin inflammation were clinically (PASI score) and histopathologically evaluated. The immunological changes induced by IMQ treatment in lymphocyte populations from peripheral blood and spleen were evaluated by flow cytometry. The main changes observed in peripheral blood were the significantly increased T-CD8a+ lymphocyte and NK1.1+ cell percentages and the decreased T-CD4+ and B lymphocyte percentages in IMQ-treated mice. In spleen samples, lymphocytes showed the same tendency of variation as in peripheral blood, but without statistical significance. A significant decrease of B cells percentages was observed in spleen suspensions. Data obtained in skin samples may suggest the involvement of CD3ε+, CD4+ and CD8a+ cells in the lesional process. This murine model was analyzed by performing a basic cellular profile at three levels: peripheral blood, spleen and skin. The evaluation aimed to establish the immune framework of this experimental model that could further be used for etipathogenic mechanism identification and/or for studies regarding targeted therapies.

Role of Innate Immune Cells in Psoriasis

“…In the imiquimod-induced psoriasis-like dermatitis mouse model, NK cells are decreased in the peripheral blood and spleen [108]. However, the role of NK cells in psoriasis mouse models remains unclear, although NK cell maturation markers, such as CD11b, CD43, CD27, and killer cell lectin-like receptor G1 (KLRG1), increase in peripheral blood and spleen NK cells from imiquimod-treated mice [109].…”

Reinforcing involvement of NK cells in psoriasiform dermatitis animal model

“…IMQ-based mouse model of psoriasiform dermatitis was replicated according to the protocols described by us (34), by applying a daily topical dose of Aldara cream on the shaved back skin of C57BL/6 mice for 5 consecutive days. 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.…”

“…Our prior published results using IMQ animal model showed that there is a clear alteration of lymphocyte percentages in peripheral blood (PB) and in secondary organs, pinpointing towards NK lymphocyte deregulation (34). As NK cells are one of the main immune populations that balance innate and adaptive immunity we enlarged the evaluated subtypes of NK subpopulations identified in PB and in secondary lymph organs seeking to establish the best pattern of NK phenotype related to the evolution of psoriatic lesions.…”

Advances in Understanding the Immunological Pathways in Psoriasis

“…Deficiency of VISTA (V-domain Immunoglobulin Suppressor of T cell Activation), an inhibitory immune checkpoint protein which suppresses CD4+ and CD8+ T cell activation, was also associated with exacerbated psoriasiform inflammation due to hyperactivation of Erk1/2 and Jnk1/2 and increased production of IL-23 [108]. In an imiquimod-induced psoriatic mouse model, Surcel et al have shown that in both peripheral blood and secondary lymphoid organs disease development is associated with a significantly increased T-CD8a+ and NK1.1+ cell percentages while decreased T-CD4+ and B lymphocyte percentages [109]. Furthermore, the deficiency of TWEAK, a molecule of the TNF superfamily [110], the overexpression of Glucocorticoid-induced Leucine Zipper (GILZ) [111], prokineticin 2 (PK2) [112], upregulation of ANGPTL6 [113], Human β-Defensin 3 and Murine β-Defensin [114] were shown to have an inflammatory effect while the natural plant antimicrobial solution (PAM) [115], the endoribonuclease MCPIP1 [33], the flavone Luteolin-7-glucoside (LUT-7G) [46], Heme oxygenase-1 (HO-1) [116], the flavonoid Astilbin [117], Paeoniflorin (PF) and Paeonol (PN)-ingredients from plants used in Traditional Chinese Medicine [118,119], superoxide dismutase (SOD3)-transduced Mesenchymal Stem Cells [120] have an anti-inflammatory effect.…”