组织定居Langerhans细胞在银屑病中的负向免疫调控作用及机制研究

银屑病发病机制复杂，皮肤免疫系统的平衡紊乱是重要机制。Langerhans 细胞（LCs）具重要免疫调控作用，参与维持皮肤免疫稳态。LCs可分为组织定居LCs（cLCs）和单核来源LCs（MoLCs）两亚群，研究发现MoLCs具促进银屑病作用，而cLCs作用不明。我们利用缺失LCs的转基因小鼠，通过骨髓移植构建表皮内分别只含cLCs和MoLCs的嵌合小鼠，诱导银屑病模型，发现只含cLCs的小鼠炎症最弱。由此我们提出假说：银屑病局部cLCs数量和功能异常，造成负向免疫调控机制缺陷，发生Treg功能低下、效应性T细胞异常活化等免疫微环境紊乱，从而导致银屑病发病。本研究拟深入分析cLCs在银屑病中的数量、表型、应答等特点，分析其对Treg数量、活性及分泌细胞因子的影响，利用Treg缺失小鼠分析cLCs的数量和功能，揭示cLCs发挥负向调控的机制。项目的实施有望为银屑病发病机制及治疗提供新的思路。

The pathogenesis of psoriasis is complex, and the balance disorder of skin immune system is an important mechanism. Langerhans cell (LCs)plays an important role in immune regulation and is involved in maintaining skin immune homeostasis. LCs have two different subsets, classical LCs(cLCs) and monocytes derived LCs(Mo-LCs). The study found that MoLCs plays a role in promoting psoriasis development, while the role of cLCs is still unknown. Using LCs constitutively deficient mice, we produce chimeric mice, which only have cLCs and MoLCs whin epidermis respectively, and then induce psoriasis model. We found that the chimic mice only containing cLCs in epidermis gained the weakest inflammation. Thus, we hypothesize that abnormal number and/or function of local cLCs in psoriasis caused negative immune regulation mechanism defects, which contributed to immune microenvironment disorder，such as regulatory T cells (Treg) hypofunction and effect T cell abnormal activation, and lead to the onset of psoriasis. We plan to analyze the phenotype, migration, response characteristics of cLCs, and the impact of cLCs on the number, activity and cell factor secretion of Treg, and effector T cells. Then we analyze the number and function of cLCs using Treg defect mouse, and further explore the role and mechanism of cLCs in the pathogenesis of psoriasis from the perspective of Treg. The implementation of the study is expected to provide new ideas for the pathogenesis and treatment of psoriasis.