The cell-specific role of Interferon regulatory factor-5 for tumor cell plasticity and tumor progression during ulcerative colitis-associated and spontaneous colon tumorigenesis

溃疡性结肠炎（UC）是一个众所周知的风险因素，发展为结直肠癌（CRC）。关于UC，全基因组关联研究（GWAS）和候选基因研究已经确定了多种易感基因座。特别是，对六个UC GWAS数据集进行的荟萃分析确定了其他风险位点，包括干扰素调节因子-5（IRF-5）。IRF-5作为1型干扰素的转录激活因子发挥作用，因此能够调节编码对精氨酸诱导的细胞可塑性、细胞增殖和分化具有不同影响的蛋白质的多个基因。我们现在可以证明IRF-5在UC、结肠炎相关结直肠癌（CAC）和散发性CRC中的表达。IRF-5的表达不限于特定的细胞类型，并且在个体间变化，因为结肠直肠癌细胞、T细胞、B细胞、巨噬细胞以及肿瘤细胞潜在地表达IRF-5。几个指标，包括我们自己在小鼠和人类疾病中的初步工作，表明IRF-5在结直肠癌发展中的病理学意义。该项目的目的是证明IRF-5在肠道肿瘤发生中的细胞类型特异性作用。

Ulcerative colitis (UC) is a well-known risk factor for the development of colorectal cancer (CRC). With regards to UC genome-wide association studies (GWAS) and candidate gene studies have identified a variety of susceptibility loci. In particular, a conducted meta-analysis of six UC GWAS datasets additional risk loci, including Interferon regulatory factor-5 (IRF-5), were identified. IRF-5 functions as transcriptional activators for type-1 interferons and, thus, is capable of modulating multiple genes that encode proteins with diverse effects on cytokine-induced cell plasticity, cell proliferation and differentiation. We can now demonstrate the expression of IRF-5 in UC, colitis-associated colorectal cancer (CAC) and in sporadic CRC. The expression of IRF-5 is not limited to a particular cell type and varies interindividually, as colorectal cancer cells, T cells, B cells, macrophages, as well as tumor cells potentially express IRF-5. Several indicators, including our own preliminary work in mice and human disease, suggest a pathological significance of IRF-5 in the development of colorectal carcinomas. The aim of this project is to demonstrate cell type-specific roles of IRF-5 in intestinal tumorigenesis.