CXCL13, also known as C-X-C motif ligand 13, is a B-cell chemokine. It binds to its receptor CXCR5, building a signaling network that plays a vital role in the immune system. It is involved in lymphoid neogenesis, lymphoid organization, and immune responses [1,2]. The CXCL13/CXCR5 axis is associated with multiple pathways related to immune-mediated processes and has overall biological importance in maintaining normal immune function and in disease pathogenesis. Genetic models, such as KO/CKO mouse models, can be valuable for studying CXCL13's functions.

In a spinal nerve ligation (SNL) mouse model of neuropathic pain, CXCL13 was persistently upregulated in spinal cord neurons, leading to spinal astrocyte activation via CXCR5. shRNA-mediated inhibition of CXCL13 in the spinal cord attenuated SNL-induced neuropathic pain. Also, CXCR5-deficient (Cxcr5-/ -) mice did not experience neuropathic pain, highlighting the role of the CXCL13/CXCR5 axis in neuropathic pain development [3]. In multiple myeloma, mice inoculated with CXCL13-silenced MM cells developed lower bone marrow disease, with reduced M2 macrophage polarization, decreased bone disease, and lower expression of osteoclast-associated genes, suggesting CXCL13's role in multiple myeloma progression [4].

In conclusion, CXCL13 is essential for immune-related functions through its interaction with CXCR5. Model-based research, especially using KO/CKO mouse models, has revealed its significance in diseases like neuropathic pain and multiple myeloma. These findings contribute to understanding the biological processes underlying these diseases and may provide potential therapeutic targets for treatment.

References:

1. Pan, Zijian, Zhu, Tong, Liu, Yanjun, Zhang, Nannan. 2022. Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases. In Frontiers in immunology, 13, 850998. doi:10.3389/fimmu.2022.850998. https://pubmed.ncbi.nlm.nih.gov/35309354/

2. Wang, Binhan, Wang, Manni, Ao, Danyi, Wei, Xiawei. 2022. CXCL13-CXCR5 axis: Regulation in inflammatory diseases and cancer. In Biochimica et biophysica acta. Reviews on cancer, 1877, 188799. doi:10.1016/j.bbcan.2022.188799. https://pubmed.ncbi.nlm.nih.gov/36103908/

3. Jiang, Bao-Chun, Cao, De-Li, Zhang, Xin, Ji, Ru-Rong, Gao, Yong-Jing. 2016. CXCL13 drives spinal astrocyte activation and neuropathic pain via CXCR5. In The Journal of clinical investigation, 126, 745-61. doi:10.1172/JCI81950. https://pubmed.ncbi.nlm.nih.gov/26752644/

4. Beider, Katia, Voevoda-Dimenshtein, Valeria, Zoabi, Ali, Peled, Amnon, Nagler, Arnon. 2022. CXCL13 chemokine is a novel player in multiple myeloma osteolytic microenvironment, M2 macrophage polarization, and tumor progression. In Journal of hematology & oncology, 15, 144. doi:10.1186/s13045-022-01366-5. https://pubmed.ncbi.nlm.nih.gov/36217194/