NCAM1通过Ca2+-CaN-NFATc通路活化NKT细胞在精神因素影响口腔扁平苔藓发生发展中的作用及机制研究

口腔扁平苔藓（OLP）是T细胞介导的慢性免疫炎性疾病，发病率高且有癌变风险，临床治疗策略尚待完善。精神因素作为重要病因与疾病进程密切相关，然而其促发OLP的机制不清。课题组前期首次挖掘出OLP与精神因素强关联基因神经细胞黏附分子1(NCAM1)，其编码蛋白CD56是NK及NKT细胞表面标志物，可通过同嗜性细胞黏着介导NKT细胞活化放大免疫反应。预实验发现OLP病损处富集CD56+NK及NKT细胞，且与精神因素及神经递质5-HT等表达成正相关，提示CD56可能是精神因素影响OLP发生免疫应答紊乱的中间关键分子。因此提出：精神因素通过5-HT等调控CD56表达，通过同嗜性细胞黏着NK细胞介导NKT细胞活化，促进OLP免疫炎症进程的科学假说。项目以关键分子NCAM1/CD56为切入点，从临床-病理-细胞多层面深入解析精神因素介导OLP进程的全新神经免疫调控机制，为OLP治疗提供新靶点和新思路。

Oral lichen planus (OLP) is a T cell-mediated chronic immune inflammatory disease with high incidence and cancer risk. The clinical treatment strategy remains to be improved. As an important etiology, mental factors are closely related to the disease process, but the mechanism of OLP is unclear. In the early stage, the research group discovered for the first time the gene neural cell adhesion molecule1 (NCAM1), which is strongly associated with OLP and mental factors. Pre-experiments found that CD56+NKT and NK cells were enriched in OLP lesion, and were positively correlated with the expression of mental factors and the psychological stress molecule 5-HT, suggesting that CD56 may be a key intermediate molecule for mental factors to affect the immune response disorder of OLP. Therefore, the scientific hypothesis of OLP immune inflammatory process is proposed that mental factors regulate the expression of CD56 through 5-HT, mediate NKT cells activation through homophilic cell adhesion to NK cells. The project takes the key molecule NCAM1/CD56 as the starting point, and deeply analyzes the new neuroimmune regulation mechanism of mental factors mediated OLP process from the clinical-pathological-cellular multi-level, and provides new targets and new ideas for OLP treatment.