TREM-1/PI3K/Akt信号通路在肠道菌群紊乱促进银屑病发生中的作用和机制研究

肠道菌群紊乱与银屑病发生密切相关，但具体分子机制尚不明确。文献报道肠道菌群紊乱可导致体内TREM-1活化，激化炎症反应。我们前期发现TREM-1在银屑病皮损中表达升高，LPS可诱导角质形成细胞中TREM-1表达，同时伴随PI3K/Akt通路激活。因此我们推测：肠道菌群紊乱可通过激活皮肤组织中TREM-1/PI3K/Akt信号通路导致炎症微环境形成，诱导单核细胞分化，促进银屑病发展。本项目首先分析银屑病患者肠道菌群结构，以及TRME-1通路蛋白表达水平与疾病严重程度相关性；其次阐明角质形成细胞中TREM-1通过PI3K/Akt转导通路调控炎症微环境形成的分子机制，并建立共培养体系明确对单核细胞分化的影响；最后通过粪菌移植银屑病小鼠模型，验证肠道菌群紊乱通过TREM-1信号通路促进银屑病发生的作用机制。本课题有助于阐明肠道菌群在银屑病发病中的作用机制，为疾病的诊治提供新的研究思路和作用靶点。

Gut microbiota dysbiosis triggers and exacerbates psoriatic lesions. However, the precise mechanism has not been elucidated yet. Recent studies demonstrated TREM-1 is elevated in patients with microbiota dysbiosis, and aggravates inflammatory responses. Our preliminary data showed that TREM-1 is increased in patients with psoriasis and LPS-induced the expression of TREM-1 in keratinocytes accompanied with activation of PI3K/Akt pathway. Thus, we hypothesize that gut microbiota dysbiosis activates the TREM-1 signal pathway to form inflammatory microenvironment, which further promotes the differentiation of monocytes, and amplifies psoriatic inflammation. This project intends to analyze the change of intestinal flora in patients with psoriasis, identifying the relationship between TREM-1 expression and the severity of disease. Moreover, the molecular mechanism of TREM-1 promoting inflammatory microenvironment through PI3K/Akt signaling pathway will be elucidated. Co-culture experiment clarifies the influence of TREM-1 on the differentiation of monocytes. Finally, the role of TREM-1 in the gut microbiota dysbiosis associated psoriasis will be verified by fecal microbiota transplantation of animal experiments. The results from this study will help explore the mechanism underlying gut microbiota dysbiosis in psoriasis, and even provide novel strategies for the diagnosis and treatment of patients.