Ahrr, also known as Aryl-Hydrocarbon Receptor Repressor, is a key regulator in multiple biological processes. It participates in the aryl-hydrocarbon receptor (AHR) pathway, and its protein regulates cellular toxicity through the TCDD-mediated AHR pathway [1]. Ahrr is also involved in regulating cellular growth and differentiation, which are fundamental to lip and palatogenesis [1].

Ahrr-null (Ahrr-/-) mouse models have shown that AHRR deficiency reduces the representation of intestinal intraepithelial lymphocytes (IELs) in a cell-intrinsic manner, leading to increased oxidative stress, lipid peroxidation, and ferroptosis in IELs due to the unleashed AHR-induced expression of CYP1A1 [2]. In head and neck cancer, AHRR wild-type (Ahrr + / + ) transgenic mice develop tumors more frequently, suggesting that AHRR activates the EPAS1/VEGFD signaling axis to contribute to inflammatory lymphangiogenesis [3].

In conclusion, Ahrr plays essential roles in regulating cellular toxicity, growth, and differentiation. Studies using Ahrr-/-mouse models have revealed its significance in intestinal immune responses and cancer-related processes such as lymphangiogenesis, providing insights into the mechanisms underlying related diseases.

References:

1. Linnenkamp, Bianca Domit Werner, Raskin, Salmo, Esposito, Selene Elifio, Herai, Roberto Hirochi. 2020. A comprehensive analysis of AHRR gene as a candidate for cleft lip with or without cleft palate. In Mutation research. Reviews in mutation research, 785, 108319. doi:10.1016/j.mrrev.2020.108319. https://pubmed.ncbi.nlm.nih.gov/32800270/

2. Panda, Santosh K, Peng, Vincent, Sudan, Raki, Cella, Marina, Colonna, Marco. 2023. Repression of the aryl-hydrocarbon receptor prevents oxidative stress and ferroptosis of intestinal intraepithelial lymphocytes. In Immunity, 56, 797-812.e4. doi:10.1016/j.immuni.2023.01.023. https://pubmed.ncbi.nlm.nih.gov/36801011/

3. Hu, An, Zhang, Jian-Wei, Yang, Li-Yun, Qiao, Pei-Pei, Lu, Dan. 2022. AHRR contributes to inflammatory lymphangiogenesis by activating the EPAS1/VEGFD signaling axis in head and neck cancer. In American journal of cancer research, 12, 537-548. doi:. https://pubmed.ncbi.nlm.nih.gov/35261785/