CXCL13, also known as C-X-C motif ligand 13, is a B-cell chemokine. It plays a vital role in lymphoid neogenesis, lymphoid organization, and immune responses by binding to its receptor CXCR5, building a significant signaling network [1,2]. This chemokine is mainly produced by mesenchymal lymphoid tissue organizer cells, follicular dendritic cells, and human T follicular helper cells in normal conditions, while in disease states, it can be ectopically expressed by human peripheral helper T cells and macrophages in non-lymphoid tissues [1,4].

In a spinal nerve ligation (SNL) model of neuropathic pain, CXCL13 was persistently upregulated in spinal cord neurons, leading to spinal astrocyte activation via CXCR5 in mice. shRNA-mediated inhibition of CXCL13 in the spinal cord attenuated SNL-induced neuropathic pain. Also, CXCR5-deficient (Cxcr5-/-) mice did not experience neuropathic pain, suggesting a crucial role of the CXCL13/CXCR5 axis in neuropathic pain [3]. In multiple myeloma, myeloid cells in the MM-infiltrated bone marrow were the main source of increased murine CXCL13. Mice inoculated with CXCL13-silenced MM cells developed less bone marrow disease, indicating CXCL13's role in MM progression [5].

In conclusion, CXCL13 is essential for normal immune-related processes such as lymphoid development and immune responses. Its study through models like gene-knockout mouse models has revealed its significance in diseases like neuropathic pain and multiple myeloma. These models help in understanding how CXCL13 contributes to disease pathogenesis, potentially guiding the development of new therapeutic strategies targeting the CXCL13/CXCR5 axis for these conditions.

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. Hui, Lu, Li, Ye, Huang, Meng-Ke, Jiang, Yong-Mei, Liu, Ting. 2024. CXCL13: a common target for immune-mediated inflammatory diseases. In Clinical and experimental medicine, 24, 244. doi:10.1007/s10238-024-01508-8. https://pubmed.ncbi.nlm.nih.gov/39443356/

5. 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/