Novel CATERPILLER gene involved in mucosal inflammation

描述（由申请人提供）：CATERPILLER蛋白含有n端效应域、核苷酸结合域和一系列富含亮氨酸的重复序列。这些蛋白在免疫反应中很重要，并且与多种疾病相关，包括MHCT2A、ClAS和NOD2/CARD15。NOD2/CARD15突变仅与一部分克罗恩病患者相关。克罗恩病和溃疡性结肠炎是复杂的慢性疾病，被称为炎症性肠病（IBD）。目前的观点认为，IBD是由对肠道特有菌群的异常免疫反应引起的。我们筛选了几种新的CATERPILLER基因的表达谱，以确定这些基因是否在小鼠IBD模型中受到影响。与GF动物相比，SPF条件下饲养的ILl0-/-小鼠结肠和盲肠中的16.1/NOD27表达上调（约100倍）。16.1/NOD27的上调与横结肠体内自发IL-12分泌相关。生化分析表明，16.1/NOD27是NF-K B依赖性基因表达的调节因子。这些数据表明16.1/NOD27在与活动性结肠炎相关的炎症反应中起作用。

DESCRIPTION (provided by applicant): CATERPILLER proteins contain N-terminal effector domains, a nucleotide binding domain and a series of leucine rich repeats. These proteins are important in immune responses and disease associations have been linked to several, including MHCT2A, ClAS and NOD2/CARD15. Mutations in NOD2/CARD15 are associated exclusively with a subset of Crohn's disease patients. Crohn's disease and ulcerative colitis are complex and chronic disorders that are referred to as inflammatory bowel disease (IBD). Current dogma suggests that IBD results from aberrant immune responses to endemic microflora of the gut. We screened the expression profile of several novel CATERPILLER genes to determine if these genes were influenced in a mouse model for IBD. 16.1/NOD27 was shown to be upregulated ( approximately 100 fold) in the colon and cecum of ILl0-/-mice reared under SPF conditions relative to GF animals. Upregulation of 16.1/NOD27 correlated with spontaneous ex vivo IL-12 secretion of the transverse colon. Biochemical analysis of 16.1/NOD27 has shown it to be a regulator of NF-K B dependent gene expression. These data suggest a role for 16.1/NOD27 in the inflammatory response associated with active colitis.