Cxcr6 is a chemokine receptor that binds to CXCL16, which exists in membrane or soluble form. It is a marker for resident memory T (TRM) cells and plays a role in immunosurveillance through interaction with epithelial cells. The CXCR6/CXCL16 axis is involved in multiple biological processes and disease-related pathways [1,4,5]. Genetic models, such as knockout (KO) mice, are valuable for studying Cxcr6 function.

In KO mouse models, deficiency in Cxcr6 or blocking its interaction with CXCL16 leads to poorer control of tumor proliferation by CD8+ T cells and NKT cells, especially in the liver [1]. Also, Cxcr6 deficiency impairs the accumulation, tissue residency programming, and clonal expansion of brain PD-1+CD8+ T cells, increasing pro-inflammatory cytokine production from microglia in a mouse model of Alzheimer's disease [2]. In addition, the conversion of stem-like into effector-like CTLs involves upregulation of CXCR6, and CXCR6 expression is critical for the survival and local expansion of effector-like CTLs in the tumor microenvironment [3].

In conclusion, Cxcr6 is essential for the function of various immune cells, especially T cells, in processes like immunosurveillance, tumor control, and maintaining tissue homeostasis in the brain. The use of Cxcr6 KO mouse models has revealed its significance in cancer and neurodegenerative disease, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Mabrouk, Nesrine, Tran, Thi, Sam, Ikuan, Fabre, Elizabeth, Tartour, Eric. 2022. CXCR6 expressing T cells: Functions and role in the control of tumors. In Frontiers in immunology, 13, 1022136. doi:10.3389/fimmu.2022.1022136. https://pubmed.ncbi.nlm.nih.gov/36311728/

2. Su, Wei, Saravia, Jordy, Risch, Isabel, Peng, Junmin, Chi, Hongbo. 2023. CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer's disease pathology. In Nature immunology, 24, 1735-1747. doi:10.1038/s41590-023-01604-z. https://pubmed.ncbi.nlm.nih.gov/37679549/

3. Di Pilato, Mauro, Kfuri-Rubens, Raphael, Pruessmann, Jasper N, Pittet, Mikael J, Mempel, Thorsten R. 2021. CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment. In Cell, 184, 4512-4530.e22. doi:10.1016/j.cell.2021.07.015. https://pubmed.ncbi.nlm.nih.gov/34343496/

4. Bao, Nandi, Fu, Bo, Zhong, Xiaoling, Xu, Shiping, Li, Tingting. 2023. Role of the CXCR6/CXCL16 axis in autoimmune diseases. In International immunopharmacology, 121, 110530. doi:10.1016/j.intimp.2023.110530. https://pubmed.ncbi.nlm.nih.gov/37348231/

5. Wang, Fang-Tao, Wu, Tian-Qi, Lin, Yin, Yin, Lu, Chen, Chun-Qiu. 2024. The role of the CXCR6/CXCL16 axis in the pathogenesis of fibrotic disease. In International immunopharmacology, 132, 112015. doi:10.1016/j.intimp.2024.112015. https://pubmed.ncbi.nlm.nih.gov/38608478/