CARD9介导的信号通路与肠道真菌在克罗恩病发病机制中的研究

全基因组关联研究（GWAS）报道CARD9基因的多态性与克罗恩病（CD）密切相关。CARD9 作为一个重要的衔接蛋白，连接真菌酵母多糖活化的Dectin/syk信号到BCL10-Malt1复合体，导致NF-κB激活，促进TNFα、IL10等细胞因子释放，参与抗真菌的天然免疫应答和获得性免疫应答。正常情况下，机体对肠道菌群处于免疫耐受状态,而携带该易感位点的个体，可能对肠腔内真菌免疫反应过强，导致肠道持续发生炎症反应。抗酿酒酵母菌抗体（ASCA）是 CD具有高度特异性的血清学标志物，提示肠道真菌可能和CD发病有关。本课题拟通过CARD9基因的变异将肠道真菌与CD发病联系起来，研究CARD9介导的抗真菌免疫的信号通路与肠道真菌在CD发病中的作用，从一个崭新的视角为CD发病机制的研究提供思路。

A recent Genome-wide association studies (GWAS) identified the non-synonymous single nucleotide polymorphism nsSNP rs4077515 in CARD9 is associated with Crohn's disease (CD).This SNP leads to an amino acid substitution from a serine to an asparagine residue,which maybe influenced CARD9 function. Caspase recruitment domain protein 9 (CARD9) plays an essential role in anti-fungus immunity.As an important adapter protein, CARD9 connects zymosan activation of Dectin/syk of signals to the BCL10-Malt1 complex, leading to NF-κB activation and the release of cytokines such as TNFα , IL10,etc.The host with this susceptibility locus is triggered an impaired immune response to the intestinal fungi. Anti-Saccharomyces cerevisiae antibodies (ASCA) which is a high degree of specificity of serological markers of CD, is another strong clues that intestinal fungi may be involved in CD pathogenesis. We aim to study CARD9-mediated antifungal immune signaling pathway and intestinal fungi in CD pathogenesis, and provide a new perspective on the study of CD pathogenesis.