CXCR6 is a chemokine receptor for CXCL16, which exists in membrane or soluble forms. It is a key marker for resident memory T (TRM) cells and is involved in immunosurveillance via interactions with epithelial cells. The CXCR6/CXCL16 axis is associated with various immune-related pathways and plays an important role in maintaining tissue homeostasis and immune responses [1,2,3,6,7]. Genetic models, such as gene-knockout (KO) mouse models, have been crucial in studying CXCR6's functions.

In KO mouse models, deficiency in cxcr6 impairs the control of tumor proliferation by CD8+ T cells and NKT cells, especially in the liver, suggesting its importance in anti-tumor immunity [1]. In the context of Alzheimer's disease, Cxcr6 deficiency hinders the accumulation, tissue residency programming, and clonal expansion of brain PD-1+CD8+ T cells, leading to increased pro-inflammatory cytokine production from microglia [2]. In renal fibrosis, CXCR6+ ILC3s migrate from the intestine to the kidney via CXCL16, and targeting this pathway could potentially be a therapeutic strategy [4]. Also, in NASH, CXCR6+ CD8 T cells contribute to liver immune pathology, and IL-15-induced CXCR6 upregulation renders these cells auto-aggressive [5].

In conclusion, CXCR6 is essential for multiple biological processes, mainly in immune-mediated functions. KO mouse models have significantly contributed to understanding its role in diseases like cancer, Alzheimer's disease, renal fibrosis, and NASH. These findings provide valuable insights into potential therapeutic strategies targeting the CXCR6/CXCL16 axis for treating these diseases.