TRIM37在树突状细胞活化介导哮喘发生发展中的负性调控作用和机制研究

Activation of dendritic cells and production of inflammatory cytokines play critical roles in the development of asthma. Molecular regulatory mechanisms responsible of the activation of dendritic cells are important scientific questions in the research field of asthma. TRIM family members play important roles in the regulation of innate immune response. However, systemic investigation is still needed for TRIM family members in the regulation of asthma. Hence, we screened the expression of TRIM family members in lung dendritic cells of asthma mouse model, and found that TRIM37 expression was significantly induced in asthma. These data suggest that TRIM37 may function as a feedback regulator in asthma. Furthermore, we constructed TRIM37 conditional knockout mouse, and generated dendritic cell-specific TRIM37 knockout mouse. Asthma is significantly intensified by TRIM37 deficiency in dendritic cells. Hence, we intend to investigate the roles and underlying mechanism of TRIM37 in the regulation of dendritic cells activation and asthma progression, so as to suggest new regulatory mechanisms and therapeutic targets for the inflammation of asthma.

树突状细胞（DC）活化及炎症因子表达在哮喘发生发展中发挥关键作用，DC活化的分子调控机制是哮喘研究中的重要科学问题。TRIM家族分子在天然免疫中发挥重要调控作用，但在哮喘中尚无系统研究。申请人长期从事哮喘的临床诊治和基础研究，以第一作者发表CMI等SCI论文。本研究在前期基础上，系统筛选了哮喘小鼠疾病模型肺DC细胞中TRIM家族分子的表达改变，发现TRIM37在DC中表达显著诱导增高，提示其可能在DC活化和哮喘进展中发挥反馈性调控功能。据此，我们构建了TRIM37的条件型基因敲除小鼠，并与CD11c-Cre小鼠杂交，获得了DC细胞特异性TRIM37敲除小鼠。在此小鼠中我们发现，DC细胞特异性TRIM37敲除显著促进了哮喘疾病进展，DC细胞活化显著增高。由此，本研究拟探求TRIM37在DC细胞活化及炎症因子表达中的调控作用和机制，及其在哮喘进展中的作用，以期为哮喘提出发病新机制和干预新靶点。

树突状细胞（DC）活化及炎症因子表达在哮喘发生发展中发挥关键作用，DC活化的分子调控机制是哮喘研究中的重要科学问题。TRIM家族分子在天然免疫中发挥重要调控作用，但在哮喘中尚无系统研究。本研究在前期基础上，系统筛选了哮喘小鼠疾病模型肺DC细胞中TRIM家族分子的表达改变，发现TRIM37在DC中表达显著诱导增高，提示其可能在DC活化和哮喘进展中发挥反馈性调控功能。据此，我们构建了TRIM37的条件型基因敲除小鼠，并与CD11c-Cre小鼠杂交，获得了DC细胞特异性TRIM37敲除小鼠。在此小鼠中我们发现，DC细胞特异性TRIM37敲除显著促进了哮喘疾病进展，DC细胞活化显著增高。由此，本研究探求了TRIM37在DC细胞活化及炎症因子表达中的调控作用和机制，及其在哮喘进展中的作用，以期为哮喘提出发病新机制和干预新靶点。