The role of 5-lipooxygenase expressing cells in homeostasis, injury, and colitis-associated cancer
Abstract
Patients with prolonged ulcerative colitis (UC) exposure are 20% more likely to develop colorectal cancer (CRC). Tuft cells, a rare epithelial cell type within the intestinal crypt, may be the origin of colitis-associated cancer (CAC). Furthermore, myeloid cells have been shown to impact CAC initiation. Currently, there are no models that enable the simultaneous study of intestinal tuft cells and myeloid cells. Therefore, we generated a new transgenic mouse model 5-LO-GFP-DTR-CreERT2, wherein tuft cells and bone marrow cells are marked by 5-lipoxygenase (5-LO) expression. At baseline, immunofluorescent staining of the colon, small intestine, and bone marrow show frequent transgene expression with up to 7 GFP+ cells/100 crypts, 3 GFP+ cells/100 crypts, and 30% of total bone marrow cells, respectively. During colitis, there is a loss of 5-LO+ tuft cells. In highly inflamed regions of colitis, 5-LO+ immune cells can infiltrate the colonic stroma. In rare occurrences, APC mutant 5-LO+ cells can give rise to CAC adenomas. Overall, the 5-GDC model is a complex model that can be used to gain insight into the specific role of myeloid cells and intestinal tuft cells in colitis and CAC.