Th1/Th2免疫失衡是哮喘发病最主要的免疫学机制。研究显示，DC在诱导Th2细胞分化中发挥重要作用，但何种分子通过何种机制诱导DC对T细胞的分化不甚明晰。本项目的预初实验提示：哮喘患者体内DC高表达March1这一E3泛素连接酶，并且March1上调的同时伴随着HDAC11的下调，而过表达HDAC11抑制了DC中OX40L的表达。同时，我们的实验进一步证实，March1可正调控OX40L表达并诱导Th2分化。由此我们推测，哮喘中March1通过泛素化降解HDAC11，进而解除了HDAC11对OX40L的转录抑制，最终导致DC诱导T细胞向Th2方向分化。本项目拟在现有预初实验的基础上，通过体内外实验，进一步从分子水平详细阐明DC中March1诱导Th2分化的作用及具体分子机制，为临床哮喘的诊疗提供新的理论依据和治疗靶点。

The Th1/Th2 imbalance is the most important immunological mechanism of asthma. Studies have confirmed that dendritic cell (DC) can promote the Th2 cell differentiation to induce asthma. However, the regulatory mechanism has not been fully elucidated. Our previous studies have found that the expression of March1 in DC of asthma was significantly increased, along with the down-regulation of HDAC11 (an ubiquitination substrate of March1), which negatively regulate OX40L expression. Furthermore, we have demonstrated that March1 could positively regulate the expression of OX40L and promote the differentiation of Th2 cells. Therefore, we speculate that March1 in DC promotes ubiquitination and degradation of HDAC11, further promotes the expression of OX40L and the differentiation of Th2 cells. In this study, we aim to investigate the molecular mechanism of how March1 induce the differentiation of Th2 cells in vivo and in vitro. This study will offer a new theory and target for the diagnosis and treatment of asthma.