Langerhans细胞在皮肤菌群调控接触性超敏反应中的作用及机制研究

The commensals play an important role in the development and maintenance of a healthy immune system. It's closely related to a lots of diseases. So far, most of work has focused on the gut commensals. The skin commensals are receiving more and more attention and its importance cannot be ignored. Recently, some studies have found that skin commensals can affect the maturation of local skin immune system and participart in the immune response of skin infection and injury. These revealed the important role of skin commensals. Our group established a new skin partially enclosed sterile mouse model and found that CHS of these mouse is significantly was enhansed. It indicated the skin commensals can inhibit CHS. We also fonud that after the deletion of LCs, the inhibition effect of skin commensals is weakened. These indicated that LCs participate in the process of skin commensals mediated immune response. Based on the previous work, we are going to use the skin partially enclosed sterile mouse model and LCs-deleted mouse model to analyze the role and mechanism of LCs in sensing and transducing the commensals signal, mediating the activation of dermal DC and T cell. We are going to study the mechanism of LCs-Keratinocyte. We are to actively explore and elucidate the mechanism of skin commensals regulating immune response and provide new insights into the prevention and treatment of skin diseases in future.

共生菌群对于机体免疫系统发育和功能维持具有至关重要的作用，与诸多疾病相关，目前研究主要集中在肠道菌群，皮肤菌群刚刚被关注，但其重要性同样不容忽视。最近研究发现皮肤常驻菌影响皮肤局部免疫系统的成熟，参与对感染和外伤的免疫应答，揭示了皮肤菌群的重要意义。本研究组建立了新的局部皮肤无菌小鼠模型，发现无菌皮肤介导的接触性超敏反应显著增强，提示皮肤菌群的存在抑制接触性超敏反应；同时发现Langerhans细胞(LCs)缺失小鼠，皮肤菌群对接触性超敏反应的抑制作用减弱，提示LCs参与皮肤菌群介导免疫应答。在以往工作基础上，本研究拟继续利用局部皮肤无菌小鼠模型以及LCs缺失小鼠模型，分析LCs在感知和传递皮肤菌群信号、介导真皮树突状细胞和T细胞活化中的作用及其机制，研究LCs-角质形成细胞相互作用及其机制。为阐明皮肤菌群调控免疫应答的机制进行积极地探索，为下一步菌群用于皮肤疾病的预防和治疗提供新思路。

共生菌群对于机体免疫系统发育和功能维持具有至关重要的作用，与诸多疾病相关，目前研究主要集中在肠道菌群，皮肤菌群刚刚被关注，但其重要性同样不容忽视。最近研究发现皮肤常驻菌影响皮肤局部免疫系统的成熟，参与对感染和外伤的免疫应答，揭示了皮肤菌群的重要意义。本研究组建立了新的局部皮肤无菌小鼠模型，发现无菌皮肤介导的接触性超敏反应显著增强，提示皮肤菌群的存在抑制接触性超敏反应；同时发现Langerhans细胞（LCs）缺失小鼠，皮肤菌群对接触性超敏反应的抑制作用减弱，提示LCs参与皮肤菌群介导免疫应答。利用上述局部皮肤菌小鼠模型，我们通过外涂共生菌群悬液挽救局部菌群构成，发现可挽救接触性超敏反应，而且这一效应呈量效相关性；进一步成分分析显示皮肤菌群发挥抑制性作用的成分来源于菌体成分。我们还进一步深入研究了LCs识别皮肤菌群的受体机制，我们构建了表达CD207-EGFP表达质粒，并成功导入HEK 293T细胞中表达，进而发现表达CD207的细胞能与表皮葡萄球菌有效结合；同时也进行了表皮葡萄球菌与游离CD207结合实验，同样获得阳性结果，提示CD207是介导皮肤菌群影响接触性超敏反应的重要受体分子。这些成果为阐明皮肤菌群调控免疫应答机制进行积极地探索，为下一步菌群用于皮肤疾病的预防和治疗提供新思路。本研究还为进一步研究皮肤菌群在银屑病等具体皮肤病病种中的角色打开了新的局面，从而为从皮肤菌群角度干预具体病种奠定了基础。