The primers of target genes (mouse).

ObjectivePsoriasis is a chronic inflammatory autoimmune disease that affects physical and mental health. Mental stress has been shown to exacerbate human psoriasis by unknown mechanism.MethodsPeripheral blood mononuclear cells (PBMCs) were collected from patients with psoriasis and mental stress-treated psoriatic mice. The expression levels of TLR9/MyD88/NF-κB pathway-related molecules were analyzed by qRT-PCR and western blotting. Histological examination of skin lesions was examined using hematoxylin-eosin staining. The ratios of Treg/CD4+T cells and Th17/Treg cells were determined by flow cytometry. The associations among mental stress, the TLR9/MyD88/NF-κB pathway, and psoriasis were explored using pharmacological inhibitors and lentiviral transfection.ResultsOur findings demonstrated a significant upregulation of TLR9/MyD88/NF-κB pathway-associated molecules in the PBMCs of psoriasis patients, accompanied by elevated expression of inflammatory factors. These observations were validated using a mouse model of psoriasis. Notably, mental stress was shown to activate the TLR9/MyD88/NF-κB pathway and enhance inflammatory factor production, while simultaneously increasing the Th17/Treg ratio and decreasing the Treg/CD4+T ratio. Therapeutic interventions including antipsychotic sertraline, pathway-specific inhibitors, and lentiviral transfection significantly ameliorated inflammatory markers and improved psoriasis severity grading.ConclusionThe results of this study demonstrates that mental stress induces inflammation and immune dysregulation, exacerbating psoriasis progression. These findings provide valuable insights into the pathophysiological mechanisms underlying psoriasis progression, particularly the mental stress-mediated immunoregulatory axis.

研究目标：银屑病（Psoriasis）是一类影响身心健康的慢性炎症性自身免疫疾病。已有研究表明，心理应激可加重人类银屑病的病情，但具体作用机制尚不明确。
研究方法：本研究采集了银屑病患者的外周血单个核细胞（Peripheral Blood Mononuclear Cells, PBMCs）以及经心理应激处理的银屑病模型小鼠样本。通过实时荧光定量聚合酶链反应（qRT-PCR）与蛋白质印迹（western blotting）分析TLR9/MyD88/NF-κB通路相关分子的表达水平；采用苏木精-伊红染色对皮肤皮损进行组织学检查；利用流式细胞术检测Treg/CD4+T细胞比值与Th17/Treg细胞比值。此外，本研究通过药理学抑制剂与慢病毒转染技术，探究了心理应激、TLR9/MyD88/NF-κB通路与银屑病三者之间的关联。
研究结果：本研究发现，银屑病患者外周血单个核细胞中TLR9/MyD88/NF-κB通路相关分子的表达显著上调，同时伴随炎症因子表达升高，该结果在银屑病小鼠模型中得到验证。值得注意的是，心理应激可激活TLR9/MyD88/NF-κB通路并促进炎症因子产生，同时升高Th17/Treg细胞比值，降低Treg/CD4+T细胞比值。包括抗精神病药物舍曲林、通路特异性抑制剂以及慢病毒转染在内的干预手段，可显著改善炎症标志物水平并缓解银屑病皮损严重程度分级。
研究结论：本研究结果表明，心理应激可通过诱导炎症反应与免疫失调加重银屑病进展。上述发现为银屑病进展的病理生理机制，尤其是心理应激介导的免疫调节通路，提供了具有价值的理论参考。