1. Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis.
- Author
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Lu Y, Zhu W, Zhang GX, Chen JC, Wang QL, Mao MY, Deng SC, Jin LP, Liu H, and Kuang YH
- Subjects
- Animals, Humans, Mice, Adenosine analogs & derivatives, Adenosine A2 Receptor Agonists pharmacology, Chemokine CXCL10 genetics, Chemokine CXCL10 metabolism, Chemokine CXCL10 immunology, Dendritic Cells immunology, Dendritic Cells drug effects, Disease Models, Animal, Imiquimod pharmacology, Keratinocytes immunology, Keratinocytes drug effects, Mice, Inbred C57BL, Mice, Knockout, Phenethylamines pharmacology, Adaptive Immunity drug effects, Immunity, Innate drug effects, Macrophage Activation drug effects, Macrophage Activation immunology, Macrophages immunology, Macrophages drug effects, Psoriasis immunology, Receptor, Adenosine A2A metabolism, Receptor, Adenosine A2A genetics
- 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., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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