Molecular analysis of IL-9 producing Th9 cells in the context of Colitis-associated cancer (CAC)

在炎症性肠病（IBD）中，发生结肠炎相关结肠癌（CAC）的风险增加。特别是，溃疡性结肠炎（CU）中结肠直肠癌的发病率增加是已知的，这取决于表现部位和炎症变化的程度。除了肠道内稳态紊乱外，具有促炎和促肿瘤作用的细胞因子对癌发生至关重要。通过在IBD中产生促炎细胞因子促进慢性炎症的CD 4+效应T细胞创造了可导致癌症起始和进展的肿瘤适宜环境。然而，将长期IBD与结直肠肿瘤联系起来的确切机制迄今为止在很大程度上尚不清楚。最近，我们已经能够识别PU.1表达T细胞，由于产生促炎细胞因子IL-9而被称为Th 9细胞，其对于溃疡性结肠炎的炎症起始是重要的。同时，我们的研究结果表明，IL-9在实验性CAC中具有促肿瘤作用，尽管调控致癌作用的分子机制仍不清楚。因此，拟议的项目旨在通过分析实验模型系统和患者组织，研究CAC中产生IL-9的Th 9细胞与散发性结直肠癌相比的功能重要性。

In inflammatory bowel disease (IBD), there is an increased risk of developing colitis-associated colon carcinoma (CAC). In particular, increased rates of colorectal carcinoma in ulcerative colitis (CU) are known, depending on the site of manifestation and the extent of the inflammatory changes. In addition to disturbed intestinal homeostasis, cytokines that have proinflammatory and tumor-promoting effects are of crucial importance for carcinogenesis. CD4 + effector T cells that promote chronic inflammation through the production of proinflammatory cytokines in IBD create a tumor-appropriate environment that can lead to cancer initiation and progression. The exact mechanisms that links a long-lasting IBD with colorectal tumors, however, are so far largely unclear. Recently, we have been able to identify PU.1-expressing T cells, termed Th9 cells due to the production of the proinflammatory cytokine IL-9, which are important for inflammatory initiation in ulcerative colitis. At the same time, our findings suggest a tumor-promoting effect of IL-9 in experimental CAC, although the molecular mechanism of action that regulates carcinogenesis is still unclear. Therefore, the proposed project aims to investigate the functional importance of IL-9-producing Th9 cells in CAC in comparison to sporadic colorectal carcinoma through analyzes in experimental model systems and patient tissue.