Adipose-Derived Mesenchymal Stromal/Stem Cells Reduce Inflammatory Responses and Partially Alleviate Skin Symptoms in Imiquimod-Induced Psoriasis-Like Dermatitis Model Mice.

Abstract

Transplantation of adipose-derived mesenchymal stromal/stem cells (ASCs) has successfully alleviated the severity of psoriasis. Although several therapeutic mechanisms of mesenchymal stromal/stem cells (MSCs) for psoriasis have been elucidated using the imiquimod (IMQ)-induced psoriasis-like dermatitis model, the effects of MSC transplantation on pathways other than the interleukin (IL)-23/T helper 17 (Th17) axis, including the IL-36 pathway, remain unclear. In this study, we aimed to investigate the efficacy of ASC transplantation for the IMQ-induced psoriasis-like dermatitis in male C57BL/6J mice, and to elucidate its effects on the IL-36 pathway as well as the IL23/Th17 axis. ASCs (2.0 × 10⁶ cells) from mouse inguinal white adipose tissue were subcutaneously injected into the dorsal skin of mice. After the topical application of IMQ cream for 5 consecutive days, objective severity scores, cytokine gene expression levels, and neutrophil infiltration grade were determined to evaluate their efficacy. Anti-IL-23p19 antibody treatment was used for comparison. ASCs slightly ameliorated IMQ-induced epidermal thickening, although anti-IL-23p19 antibodies had no effect on any skin manifestations. Anti-IL-23p19 antibody and ASC suppressed the expressions of Il17a, Il17f, and Il22 mRNAs and neutrophil infiltration in IMQ-applied skin, but not the expression of Il1f6 and Il1f9. ASC also suppressed the expressions of Il23, Il6, Il1b, Tnfa, Lipocalin-2, and Cxcl5 mRNAs, which were not suppressed by anti-IL-23p19 antibody treatment. In conclusion, ASC transplantation suppressed activation of the IL-23/Th17 axis and neutrophil infiltration, and inhibited the activation of a broader range of inflammatory mediators except for IL-36 expression in IMQ-applied skin compared with anti-IL-23p19 antibody treatment.