Abnormal inflammatory traits and downregulated caveolin-1 expression in monocytes of psoriasis patients may relate to psoriatic inflammation and atherosclerosis.. Abnormal inflammatory traits and downregulated caveolin-1 expression in monocytes of psoriasis patients may relate to psoriatic inflammation and atherosclerosis.

Background: Monocytes and macrophages are implicated in inflammation and atherosclerosis, whereas monocytes are involved in psoriasis lesion formation. We previously reported a psoriatic inflammation-associated significant decrease in the membrane protein caveolin-1 (CAV-1) in psoriasis patient monocytes. However, the phenotype of circulating monocytes and their macrophage differentiation in psoriasis patients remain unclear. Objective: We sought to clarify circulating monocyte and monocyte-derived macrophage (MDM) phenotypes in psoriasis patients with and without comorbidities. Method: Thirty-one patients with psoriasis vulgaris and 28 control subjects were included. Surface macrophage markers and inflammatory status were examined in circulating monocytes and MDMs from both groups. Expression of CD36, which mediates macrophage uptake of oxidized low-density lipoprotein (oxLDL), was evaluated in these cells. CAV-1-silenced monocytes were differentiated into macrophages to investigate the effects of CAV-1 downregulation on psoriatic inflammation and atherosclerosis. Results: Macrophage surface markers were detectable in circulating monocytes. A significant M1 shift was detected in monocytes and MDMs in psoriasis patients, including those without cardiovascular disease risk factors, as compared to controls. MDMs of psoriasis patients had more CD36-expressing cells, which are associated with atherosclerosis risk. Additionally, CAV-1-silencing in monocytes increased the likelihood of M1-biased macrophage differentiation and increased pro-inflammatory cytokine production. Conclusions: Monocytes from psoriasis patients were more likely to differentiate into M1-dominant macrophages, correlating with inflammatory status and CAV-1 expression. These aberrant inflammatory monocytes not only contribute to psoriatic inflammation by producing psoriatic cytokines, but also have a phenotype that could increase atherosclerosis risk by uptake of oxLDL and formation of foam cells. Overall design: The expression profiles of primary human macrophages from healthy donors were evaluated. The macrophages have two groups: a monocyte-derived group with suppressed Caveolin-1 (Cav-1) expression and an unsuppressed group (control).

研究背景：单核细胞与巨噬细胞参与炎症及动脉粥样硬化的发生发展，而单核细胞还参与银屑病皮损的形成。本团队此前曾报道，银屑病患者单核细胞中膜蛋白小窝蛋白-1（caveolin-1, CAV-1）的表达因银屑病炎症反应出现显著下调。然而，银屑病患者循环单核细胞的表型及其向巨噬细胞的分化过程仍未明确。
研究目的：明确伴/不伴合并症的银屑病患者循环单核细胞及单核细胞衍生巨噬细胞（monocyte-derived macrophage, MDM）的表型特征。
研究方法：本研究纳入31例寻常型银屑病患者及28名健康对照受试者。对两组人群的循环单核细胞及MDM进行检测，分析其巨噬细胞表面标志物表达及炎症状态。同时检测上述细胞中CD36的表达水平——CD36可介导巨噬细胞摄取氧化型低密度脂蛋白（oxidized low-density lipoprotein, oxLDL）。此外，将小窝蛋白-1沉默的单核细胞诱导分化为巨噬细胞，以探究小窝蛋白-1下调对银屑病炎症及动脉粥样硬化的影响。
研究结果：循环单核细胞中可检测到巨噬细胞表面标志物。与健康对照相比，银屑病患者（包括无心血管疾病危险因素的患者）的单核细胞及MDM均出现显著的M1型极化。银屑病患者的MDM中表达CD36的细胞比例更高，而该类细胞与动脉粥样硬化风险升高相关。此外，单核细胞的小窝蛋白-1沉默可增加巨噬细胞向M1型偏态分化的概率，并促进促炎细胞因子的产生。
研究结论：银屑病患者的单核细胞更易分化为以M1型为主的巨噬细胞，该现象与炎症状态及小窝蛋白-1的表达水平相关。这类异常的炎症性单核细胞不仅可通过分泌银屑病相关细胞因子参与银屑病炎症反应，还可通过摄取氧化型低密度脂蛋白形成泡沫细胞，进而表现出升高动脉粥样硬化风险的表型。
研究整体设计：本研究对健康供者来源的原代人巨噬细胞的表达谱进行了分析，将巨噬细胞分为两组：一组为小窝蛋白-1（Cav-1）表达被抑制的单核细胞衍生巨噬细胞组，另一组为未进行抑制的对照组巨噬细胞。