CXCL16, also known as C-X-C motif ligand 16, is a chemotactic cytokine belonging to the α -chemokine subfamily. It binds to the chemokine receptor CXCR6, a G protein -coupled receptor with 7 transmembrane domains. The CXCR6/CXCL16 axis plays a significant role in regulating inflammation, tissue injury, and fibrosis, and is involved in multiple biological processes such as cell adhesion, migration, and lipid scavenging [1,2,4,5].

Deletion of Cxcl16 in non -obese diabetic (NOD) mice suppressed the development of autoimmune diabetes. Mechanistically, Cxcl16 deficiency impaired clearance of oxidized low -density lipoproteins (OxLDL) by islet macrophages, 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 is crucial in various disease conditions. Its role in autoimmune diabetes, as revealed by the Cxcl16 knockout in NOD mice, shows that it can affect the immune response and lipid scavenging in pancreatic islets, potentially contributing to the pathogenesis of the disease. Understanding CXCL16's functions may provide new insights into treating related diseases.

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/