银屑病是由多种复杂因素介导的炎症性皮肤病，神经-内分泌系统紊乱引起的T细胞分化异常是其重要诱因之一。黑色素聚集激素（MCH）是具有免疫调控作用的神经肽。我们前期研究发现，银屑病患者血清中MCH水平升高。体外实验表明MCH能够促进CD4+T细胞向Th17细胞分化，抑制Treg分化，并上调T细胞脂肪酸合成酶的表达。因此提出假说：抑郁等精神因素导致神经肽MCH水平升高，进一步诱导CD4+T细胞的脂肪酸代谢重组和CD4+T细胞分化异常从而参与银屑病的发生发展。本项目拟明确MCH参与CD4+T细胞分化失衡的现象；进而通过转录组测序、生物能量代谢检测等技术，深入研究MCH活化脂肪酸合成途径调控CD4+T细胞分化的具体机制；最后利用CD4creMCHRfl/fl小鼠模型，明确MCH是CD4+T细胞异常活化的关键因子。预期结果将丰富及完善银屑病发病机制，为银屑病治疗提供新的思路。

Psoriasis is an inflammatory skin disease mediated by a variety of complex factors. Neuroendocrine system disorder is one of the main cause that derived psoriasis pathogenesis. Melanin concentrating hormone (MCH) is a neuropeptide with immunoregulatory effect. In our preliminary studies, we found higher level of MCH expression in psoriatic serums. In vitro experiments show that MCH can promote the differentiation of CD4 + T cells into Th17 cells and suppressed Treg differentiation; Additionally, MCH up-regulated the enzyme ACC1 (acetyl CoA carboxylase) activation which is critical in fatty acid synthesis. In this study, we hypothesis that depression and other mental factors lead to increased levels of neuropeptide MCH, which further induces the fatty acid metabolism reprogramming and abnormal differentiation of CD4+ T cells, so as to participate in the occurrence and development of psoriasis. This project aims to clarify the phenomenon that MCH participates in the imbalance of CD4+T cell differentiation. Furthermore, the specific mechanism of the regulation of CD4+T cell differentiation by MCH activated fatty acid synthesis pathway was studied by transcriptome sequencing and bioenergy metabolism detection. Finally, the combination of chronic restraint stress model and IMQ-induced psoriasis mice model applied to CD4creMCHRfl/fl mice will be used to confirm that MCH is the key factor of abnormal activation of CD4 + T cells. The expected results will enrich and improve the pathogenesis of psoriasis, and provide new ideas for the treatment of psoriasis.