Itln1-flox Mouse

Itln1, also known as intelectin-1 and sometimes omentin, is a carbohydrate-binding protein with diverse functions. It is secreted by intestinal epithelial cells, such as goblet cells in humans and Paneth cells in C57BL/6 mice. Itln1 is involved in innate immunity, interacting with the microbiota [1,3]. It has been implicated in multiple signaling pathways including PI3K/AKT/GSK3ß which affects the production of factors like IL-17D and CXCL2 [2]. Itln1 is important in maintaining physiological balance in processes like mucus barrier formation, and its dysregulation is associated with various diseases.

In a Itln1 knockout mouse model, mice showed increased susceptibility in an acute model of experimentally induced colitis with 2% w/v dextran sulfate sodium (DSS), suggesting that Itln1 may play a role in protecting against colitis [3]. In colorectal carcinoma, low levels of ITLN1 are correlated with obesity-related carcinogenesis. ITLN1 inhibits tumor neovascularization and myeloid-derived suppressor cells accumulation by suppressing tumor-derived IL-17D and CXCL2 through the KEAP1/Nrf2/ROS/IL-17D and p65 NF-ĸB/CXCL2 signaling cascades dependent on PI3K/AKT/GSK3ß [2]. In ovarian cancer, ITLN1 suppresses lactotransferrin's effect on cancer cell invasion and proliferation, and down-regulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates cancer progression [4]. In radiation-induced kidney injury, overexpression of ITLN1 can improve kidney function in rats by activating the Akt/GSK-3β/Nrf2 signaling pathway, suppressing oxidative stress, cell apoptosis, inflammation, cellular senescence, and fibrosis [5].

In conclusion, Itln1 plays essential roles in innate immunity, mucus barrier maintenance, and disease-related processes such as cancer and colitis. Gene knockout mouse models have been valuable in revealing its protective role in colitis, and its anti-tumor functions in colorectal and ovarian cancer. Its role in modulating radiation-induced kidney injury also shows its importance in maintaining tissue homeostasis. These findings contribute to our understanding of disease mechanisms and potential therapeutic targets.