CXCL16, a chemotactic cytokine in the α -chemokine subfamily, is also known as C-X-C motif ligand 16. It binds to the G protein-coupled receptor CXCR6, and the CXCR6/CXCL16 axis is involved in multiple biological processes, such as regulating inflammation, tissue injury, and fibrosis [1,2,4,5]. It is expressed in various immune cells and has functions related to cell adhesion, migration, and oxidized lipid scavenging [2,3].

In a non-obese diabetic (NOD) mouse model, deletion of Cxcl16 suppressed the development of autoimmune diabetes. Mechanistically, Cxcl16 deficiency in islet macrophages impaired the clearance of oxidized low-density lipoproteins (OxLDL), leading to OxLDL accumulation in pancreatic islets and a reduction in intra-islet transitory (Texint) CD8+ T cells with proliferative and effector signatures [3].

In conclusion, CXCL16 plays significant roles in various disease conditions. The Cxcl16 knockout in NOD mice reveals its role in the development of autoimmune diabetes, specifically in the process of OxLDL scavenging by islet macrophages and the subsequent differentiation of pathogenic CD8+ T cells. This indicates that CXCL16 is a key factor in understanding the pathogenesis of autoimmune diabetes and potentially other related diseases [3].

References:

1. Korbecki, Jan, Bajdak-Rusinek, Karolina, Kupnicka, Patrycja, Chlubek, Dariusz, Baranowska-Bosiacka, Irena. 2021. The Role of CXCL16 in the Pathogenesis of Cancer and Other Diseases. In International journal of molecular sciences, 22, . doi:10.3390/ijms22073490. https://pubmed.ncbi.nlm.nih.gov/33800554/

2. 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/

3. Srivastava, Neetu, Hu, Hao, Peterson, Orion J, Unanue, Emil R, Wan, Xiaoxiao. 2024. CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8+ T cells in diabetic autoimmunity. In Immunity, 57, 1629-1647.e8. doi:10.1016/j.immuni.2024.04.017. https://pubmed.ncbi.nlm.nih.gov/38754432/

4. 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/

5. Izquierdo, María Concepción, Martin-Cleary, Catalina, Fernandez-Fernandez, Beatriz, Carrero, Juan Jesús, Ortiz, Alberto. 2014. CXCL16 in kidney and cardiovascular injury. In Cytokine & growth factor reviews, 25, 317-25. doi:10.1016/j.cytogfr.2014.04.002. https://pubmed.ncbi.nlm.nih.gov/24861945/