肠黏膜异常的免疫应答是炎症性肠病（IBD）发病的关键因素之一。细胞外基质蛋白Mindin在不同免疫应答中发挥着重要作用，但其肠道炎症中的功能、细胞膜受体及调控机制尚未解明。本课题组前期发现：Mindin蛋白在IBD患者肠黏膜的炎症部位表达上调；在DSS诱导的小鼠肠炎实验中，Mindin通过TLR-9介导的方式促进黏膜炎症；并通过生物信息学预测及免疫共沉淀等方法初步证实，整合素αmβ2（CD11b/CD18）为Mindin的共同膜受体。因此本课题将：通过放射配/受体结合等技术进一步明确CD11b/CD18为Mindin的膜受体，及其诱导的生物学行为和激活的细胞内信号通路；利用本课题组已构建的Mindin基因敲除小鼠建立肠炎模型，进一步证实配/受体结合后的功能与机制，并在IBD患者临床样本上进行验证。从而阐明Mindin/ CD11b/CD18轴在IBD发病肠道异常黏膜免疫应答中的作用机制。

The abnormal immune response in intestinal mucosa is a key factor of immunopathogenesis in inflammatory bowel disease (IBD). The extracellular matrix protein Mindin has been previously demonstrated to have important functional roles both in the innate and adaptive immune responses, its function in colitis, cell membrane receptor and the involved mechanism remain poorly understood. Our previous work has demonstrated that Mindin protein is overexpressed on inflammatory area of IBD patients, plays the proinflammatory role on DSS-induced colitis in mice through TLR-9 pathway. Our preliminary results from bioinformatics prediction and Co-immunoprecipitaton showed that Mindin bind to complement receptor 3（CR3） of CD11b/CD18, αmβ2 in the cell membrane in vitro. Thus, in this study, we will further define the CD11b/CD18 was cell membrane co-receptors of ECM protein of Mindin and determine the induced biological behavior and activated downstream signaling pathway in vitro and in vivo colitis model application on the Mindin deficient mice, further confirm them on clinical tissue samples. We elucidate the function and mechanism of Mindin/CD11b/CD18 axis during intestinal immune responses of IBD.