腺苷 A2A 受体活化调节 M1 巨噬细胞的活化,从而启动银屑病的先天性免疫和适应性免疫。

IF 4.5 3区 医学 Q2 IMMUNOLOGY Clinical immunology Pub Date : 2024-07-11 DOI:10.1016/j.clim.2024.110309
Yan Lu , Wu Zhu , Guan Xiong Zhang , Jun Chen Chen , Qiao Lin Wang , Man Yun Mao , Si Chun Deng , Li Ping Jin , Hong Liu , Ye Hong Kuang
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引用次数: 0

摘要

牛皮癣是一种常见的全身性炎症性疾病,其特点是真皮层浸润的促炎性巨噬细胞(M1 巨噬细胞)被激活。M1 巨噬细胞是如何导致银屑病的仍是未知数。在这项研究中,我们发现腺苷 A2A 受体(A2AR)激动剂 CGS 21680 HCl 可通过减少 M1 的浸润来缓解咪喹莫特(IMQ)和小鼠 IL-23 蛋白(rmIL-23)诱导的银屑病炎症。相反,小鼠缺失 Adora2a 会加重银屑病样表型。从机理上讲,A2AR的激活通过NF-κB-KRT16途径抑制了M1巨噬细胞的活化,从而减少了CXCL10/11的分泌并抑制了Th1/17的分化。值得注意的是,我们的研究首次在 M1 巨噬细胞中发现了 KRT16 的表达,而不仅仅是在角质形成细胞(KCs)中。通过单细胞 RNA 测序(scRNA-Seq),首次发现 CXCL10/11 主要来源于巨噬细胞和树突状细胞(DCs),而不是银屑病中的 KCs。总之,该研究强调了 M1 作为先天性免疫细胞在银屑病发病机制中的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis

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.

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来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
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