糖蛋白Ib-CD11b + 单核细胞源性巨噬细胞介导动脉粥样硬化加重的银屑病炎症。

IF 5.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-09-11 DOI:10.1016/j.lfs.2025.123960

Canbin Dong , Wenjing Yang , Lianxi Sun , Jui-Ming Lin , Jie Wang , Yilun Wang , Lanmei Lin , Xinyi Zhu , Jia Huang , Xiaonian Lu , Junhao Zhu , Jinhua Xu , Jinyun Tan , Ningwen Zhu , Juan Du

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引用次数: 0

摘要

背景：银屑病是一种全身性炎症性皮肤病，影响全球2-3 - %的人口，具有显著的心血管合并症。银屑病与动脉粥样硬化之间存在复杂的炎症相互作用，但确切的机制尚不清楚。方法：为了阐明这种关系，我们收集了treatment-naïve合并银屑病和动脉粥样硬化的患者的皮肤活检，进行了单细胞RNA测序，并整合了公共动脉粥样硬化数据集。生物信息学分析鉴定了细胞群和相互作用。验证包括免疫组织化学、免疫荧光、分离的患者巨噬细胞和血小板的体外功能分析，以及用CD11b激动剂治疗的咪喹莫德诱导的牛皮癣小鼠体内模型。结果：单细胞RNA测序发现，伴有动脉粥样硬化的银屑病病变中CD11b + 单核细胞来源的巨噬细胞显著增加，表现出促炎M1极化和IL-17/趋化因子信号富集。这些巨噬细胞与动脉粥样硬化斑块中的单核细胞具有相同的转录特征。在体内，CD11b激动作用（ADH-503）加重了吡喹莫特诱导的银屑病炎症。从机制上讲，血小板来源的GPIb通过GPIb- cd11b轴促进巨噬细胞M1极化，证明GPIb上调与银屑病严重程度（PASI）、血管周围区域的空间共定位以及重组GPIb诱导的剂量依赖性M1标记物相关。来自动脉粥样硬化患者的GPIbhi单核细胞显示出增强的促炎通路（Th17/TNF-α），揭示了两种疾病中驱动炎症的共同机制。结论：总的来说，CD11b + 单核细胞来源的巨噬细胞通过GPIb-CD11b轴在动脉粥样硬化和牛皮癣之间的相互作用中起着核心作用。以GPIb为靶点，结合特异性药物控制动脉粥样硬化，可提高银屑病的炎症控制效果。

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Glycoprotein Ib-CD11b + monocyte-derived macrophages mediate atherosclerosis-exacerbated psoriatic inflammation

Background

Psoriasis is a systemic inflammatory skin disease affecting 2–3 % of the global population, with significant cardiovascular comorbidities. A complex inflammatory interaction exists between psoriasis and atherosclerosis, but the exact mechanism remains unclear.

Methods

To elucidate this relationship, we collected skin biopsies from treatment-naïve patients with comorbid psoriasis and atherosclerosis underwent single-cell RNA sequencing, integrated with public atherosclerosis datasets. Bioinformatics analysis identified cell populations and interactions. Validation included immunohistochemistry, immunofluorescence, in vitro functional assays with isolated patient macrophages and platelets, and an in vivo imiquimod-induced psoriasis mouse model treated with a CD11b agonist.

Results

Single-cell RNA sequencing identified significantly increased CD11b + monocyte-derived macrophages in psoriasis lesions comorbid with atherosclerosis, exhibiting proinflammatory M1 polarization and enriched IL-17/chemokine signaling. These macrophages shared transcriptional signatures with monocytes in atherosclerotic plaques. In vivo, CD11b agonism (ADH-503) exacerbated imiquimod-induced psoriatic inflammation. Mechanistically, platelet-derived GPIb promoted macrophage M1 polarization via the GPIb-CD11b axis, evidenced by GPIb upregulation correlating with psoriasis severity (PASI), spatial co-localization in perivascular regions, and dose-dependent M1 marker induction by recombinant GPIb. GPIb^hi monocytes from atherosclerotic patients showed enhanced proinflammatory pathways, revealing a shared mechanism driving inflammation in both diseases.

Conclusions

Collectively, CD11b + monocyte-derived macrophages are central to the interplay between atherosclerosis and psoriasis through the GPIb-CD11b axis. Targeting GPIb with specific drugs to control atherosclerosis may enhance the efficacy of inflammatory control in psoriasis.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.

糖蛋白Ib-CD11b + 单核细胞源性巨噬细胞介导动脉粥样硬化加重的银屑病炎症。

摘要

Background

Methods

Results

Conclusions

糖蛋白Ib-CD11b + 单核细胞源性巨噬细胞介导动脉粥样硬化加重的银屑病炎症。