New findings of macrophages in initiating and sustaining psoriasis

Abstract

Abstract Psoriasis is an immune mediated chronic inflammatory disease with an incidence rate ranging from 0.09–11.4% in the general population. Psoriasis has complex etiological factors, and its pathogenesis is still not fully understood, which poses challenges in clinical treatment. However, macrophages, acting as "sentinels" of innate immunity, have recently gained attention as a novel area of focus in immunological research on psoriasis. Recent research has found that macrophage plasticity play an important role in the initiation and maintenance of psoriasis, However, it remains underexplored how macrophage plasticity mediates the immune response to psoriasis and what the corresponding regulatory mechanism is. To investigate the involvement of macrophage polarization in the pathogenesis of psoriasis. In our study, we firstly obtained the skin gene expression dataset of both normal subjects and psoriasis patients through the GEO database, from which psoriasis patients showed a higher expression of M1 macrophage-related genes and a lower expression of M2 macrophage-related genes in skin lesions. Then, we established a mouse model of psoriasis-like dermatitis induced by Imiquimod (IMQ) and found that the macrophages in the lesions and spleen of IMQ-induced psoriasis mice were predominantly M1 macrophages. Then, we extracted primary peritoneal macrophages (PEM) from mice and induced their polarization into M1 macrophages and M2 macrophages in vitro. Intravenous infusion of M1 macrophages to IMQ-induced psoriasis-like dermatitis mice resulted in the exacerbation of psoriasis-like dermatitis in these mice. Besides, macrophage polarization was found to affect the differentiation of T cells using the RNA-seq technology. We also noticed that M1 macrophages promoted the CD4+ T cell proliferation and T helper cell 17 (Th17) differentiation and M1 macrophages could directly activate the inflammatory response of JB6 (mouse epidermal cells) independent of T cells. Taken together, this study derives new findings that M1 macrophages regulate the proliferation and differentiation of T cells and directly activate the expression of inflammatory cytokines of keratinocytes (KC) independent of T cells to participate in the occurrence and development of psoriasis. These findings provide new insights into the pathogenesis of psoriasis and identify inhibiting M1 polarization as a promising target for the treatment of this condition.