Abstract：
Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.
摘要：
银屑病是一种常见的炎症性全身性疾病，其特征是在真皮层中浸润的促炎巨噬细胞活化（M1巨噬细胞）。M1巨噬细胞如何导致牛皮癣仍然未知。在这项研究中,我们发现腺苷A2A受体(A2AR)激动剂CGS21680HCl通过减少M1浸润减轻咪喹莫特(IMQ)和小鼠IL-23蛋白(rmIL-23)诱导的银屑病炎症。相反，小鼠中的Adora2a缺失加剧了牛皮癣样表型。机械上,A2AR激活通过NF-κB-KRT16途径抑制M1巨噬细胞活化,减少CXCL10/11的分泌,抑制Th1/17分化。值得注意的是,在我们的研究中，首先在M1巨噬细胞中发现了KRT16的表达，不仅在角质形成细胞（KCs）中。使用单细胞RNA测序（scRNA-Seq），首次将CXCL10/11鉴定为主要源自巨噬细胞和树突状细胞（DC），而不是牛皮癣中的KC。总的来说,该研究强调M1作为先天免疫细胞在银屑病发病机制中的重要性。
