Ahrr, short for Aryl-Hydrocarbon Receptor Repressor, is a key gene involved in regulating the aryl-hydrocarbon receptor (AHR) pathway. AHR is a ligand-activated transcription factor, and Ahrr acts as its negative regulator. It is important in various biological processes such as cellular growth, differentiation, and regulation of cellular toxicity. Ahrr is also associated with carcinogenesis and immune-related functions [1,2].

In head and neck cancer, Ahrr-null (Ahrr-/ -) mice showed reduced tumor development frequency compared to Ahrr wild-type (Ahrr + / +) transgenic mice. This indicates that Ahrr contributes to inflammatory lymphangiogenesis by activating the EPAS1/VEGFD signaling axis in head and neck cancer [3]. In intestinal intraepithelial lymphocytes (IELs), Ahrr deficiency led to reduced IEL representation, increased oxidative stress, lipid peroxidation, and ferroptosis. Dietary supplementation with selenium or vitamin E rescued Ahrr-/-IELs, and loss of IELs in Ahrr-/-mice caused susceptibility to Clostridium difficile infection and dextran sodium-sulfate-induced colitis [2].

In conclusion, Ahrr plays crucial roles in multiple biological processes. Through gene-knockout mouse models, its functions in lymphangiogenesis in head and neck cancer and in maintaining intestinal immune responses have been revealed. Understanding Ahrr's functions provides insights into the mechanisms of related diseases and may offer potential targets for disease treatment and prevention.