脂肪细胞来源外泌体通过调控T细胞活性介导银屑病免疫紊乱

肥胖等代谢疾病常与银屑病相互伴发，是银屑病病情加重或顽固的因素，但其机制依然不明。研究表明肥胖机体脂肪细胞可通过产生含有特异性成分的外秘体，影响免疫稳态，造成代谢失衡及慢性炎症。我们发现清除肥胖小鼠外泌体可缓解咪喹莫特造成的银屑病表型，提示外泌体参与小鼠银屑病进程。用肥胖银屑病患者的血清外泌体可刺激CD4+T细胞过度增殖，提示肥胖相关外秘体可造成免疫细胞过度活化。因此我们认为脂肪细胞外泌体可造成CD4+T细胞过度活化参与银屑病免疫紊乱。本课题拟首先证实脂肪细胞外泌体在肥胖小鼠银屑病模型中发挥作用，比较肥胖与非肥胖的银屑病患者脂肪细胞外泌体对受体CD4+T细胞影响的差异，再通过小RNA测序等组学方法筛选差异MicroRNA，最后验证差异分子在银屑病免疫细胞异常活化中的作用和分子机制。项目将有助于深化对银屑病发病机制的认识，揭示代谢紊乱与银屑病的内在联系，为银屑病的系统性治疗提供理论基础。

Epidemiological studies suggest that patients with psoriasis are not only burdened with its symptoms, but also have an increased prevalence of metabolic disorders, including obesity, hypertension and cardiovascular comorbidities. It is believed that obesity has significantly risk effect on severity and manifestations of psoriasis, but the molecular linker between these two diseases is not clear. Adipocyte-derived exosomes, a very important extracellular vesicle which modulate metabolic and immune response. We hypothesis that adipocyte-derived exosome serves as a molecular linker among psoriasis and obesity based on our pre-investigations of high fat diet induced adipocyte-derived exosomes deteriorating imiquimod psoriatic phenotype . To elucidate the pathogenic functions of adipocyte-derived exosomes in psoriasis, we will study the melocular mechanism of adipocyte-derivedexosomes functions in imiquimod psoriatic mouse model. We will also investigatethe influences of exosomes on CD4+T cells and identify the specific microRNA molecules in obese psoriasis patients. Our research reveals the function of adipocyte-derived exosomes in psoriasis pathogenesis and opens a new area of psoriasis treatment strategy.