Cxcl2, also known as CXC chemokine ligand 2, is a chemokine that plays a crucial role in immune responses. It is involved in processes such as neutrophil recruitment, cell migration, and the regulation of the immune microenvironment. It exerts its functions mainly through the CXCL2-CXCR2 axis [1,2,3,4,5,6].

In mouse models, genetic deletion of Cxcl2 in NKT cells improved alveolar bone healing, indicating that Cxcl2 secreted by NKT cells inhibits osteogenic differentiation of mesenchymal stem cells and impairs alveolar bone healing [2]. In hepatocellular carcinoma, the secreted protease PRSS35 suppresses tumor progression by cleaving CXCL2, which in turn attenuates neutrophil recruitment and formation of neutrophil extracellular traps [4]. Targeting the CXCL2-CXCR2 axis in aged mice limited neutrophil migration to the liver and attenuated age-related liver injury, as Cxcl2+ macrophages in the aged liver recruit neutrophils through this axis [1].

In summary, Cxcl2 is a key chemokine in immune-related processes. Gene-knockout mouse models have revealed its role in various disease conditions, including bone regeneration, liver aging, and cancer. These findings highlight the potential of targeting Cxcl2 as a therapeutic strategy for these diseases.

References:

1. Liu, Yasong, Xiao, Jiaqi, Cai, Jianye, Zheng, Jun, Yang, Yang. 2023. Single-cell immune profiling of mouse liver aging reveals Cxcl2+ macrophages recruit neutrophils to aggravate liver injury. In Hepatology (Baltimore, Md.), 79, 589-605. doi:10.1097/HEP.0000000000000590. https://pubmed.ncbi.nlm.nih.gov/37695548/

2. Lin, Weimin, Li, Qiwen, Liu, Linfeng, Zhou, Chenchen, Yuan, Quan. 2024. Early infiltrating NKT lymphocytes attenuate bone regeneration through secretion of CXCL2. In Science advances, 10, eadl6343. doi:10.1126/sciadv.adl6343. https://pubmed.ncbi.nlm.nih.gov/38758783/

3. Zhang, Yonghui, Sang, Rui, Bao, Jingyin, Shi, Minxin, Chen, Gang. 2023. Schwann cell-derived CXCL2 contributes to cancer pain by modulating macrophage infiltration in a mouse breast cancer model. In Brain, behavior, and immunity, 109, 308-320. doi:10.1016/j.bbi.2023.02.004. https://pubmed.ncbi.nlm.nih.gov/36754246/

4. Wang, Ting, Zhou, Yingli, Zhou, Zilong, Gao, Ping, Zhang, Huafeng. 2023. Secreted protease PRSS35 suppresses hepatocellular carcinoma by disabling CXCL2-mediated neutrophil extracellular traps. In Nature communications, 14, 1513. doi:10.1038/s41467-023-37227-z. https://pubmed.ncbi.nlm.nih.gov/36934105/

5. Xu, Xingyuan, Ye, Longyun, Zhang, Qi, Ye, Mao, Liang, Tingbo. 2021. Group-2 Innate Lymphoid Cells Promote HCC Progression Through CXCL2-Neutrophil-Induced Immunosuppression. In Hepatology (Baltimore, Md.), 74, 2526-2543. doi:10.1002/hep.31855. https://pubmed.ncbi.nlm.nih.gov/33829508/

6. Nie, Fujiao, Zhang, Jie, Tian, Haoyang, Yang, Pishan, Yang, Chengzhe. 2024. The role of CXCL2-mediated crosstalk between tumor cells and macrophages in Fusobacterium nucleatum-promoted oral squamous cell carcinoma progression. In Cell death & disease, 15, 277. doi:10.1038/s41419-024-06640-7. https://pubmed.ncbi.nlm.nih.gov/38637499/