CXCL13, also known as chemokine C-X-C motif ligand 13, is a B-cell chemokine. It binds to its receptor CXCR5, building a signaling network. This axis plays a crucial role in lymphoid neogenesis, lymphoid organization, and immune responses [1,2]. It 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 [1,6].

In the context of diseases, CXCL13/CXCR5 axis has been implicated in multiple pathological conditions. In autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, etc., this axis is involved in the pathogenesis, and CXCL13 may serve as a disease biomarker and therapeutic target [1]. In cancer, CXCL13/CXCR5 signaling can modulate cancer cell growth, proliferation, invasion, and metastasis. For example, in multiple myeloma, CXCL13 is involved in M2 macrophage polarization, osteoclast activation, and tumor progression [4,5,7]. In neuropathic pain, CXCL13 in spinal cord neurons activates spinal astrocytes via CXCR5, contributing to pain development, and miR-186-5p and CXCL13/CXCR5-mediated astrocyte signaling may be therapeutic targets [3].

In conclusion, CXCL13 is a key chemokine that regulates important immune and lymphoid-related functions. Its role in various diseases, especially autoimmune diseases, cancer, and neuropathic pain, has been well-documented through functional studies. These findings suggest that targeting the CXCL13/CXCR5 axis could be a potential therapeutic strategy for these diseases.

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. Hussain, Muzammal, Adah, Dickson, Tariq, Muqddas, Zhang, Jiancun, Liu, Jinsong. 2019. CXCL13/CXCR5 signaling axis in cancer. In Life sciences, 227, 175-186. doi:10.1016/j.lfs.2019.04.053. https://pubmed.ncbi.nlm.nih.gov/31026453/

5. Hussain, Muzammal, Liu, Jinsong, Wang, Gui-Zhen, Zhou, Guang-Biao. . CXCL13 Signaling in the Tumor Microenvironment. In Advances in experimental medicine and biology, 1302, 71-90. doi:10.1007/978-3-030-62658-7_6. https://pubmed.ncbi.nlm.nih.gov/34286442/

6. 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/

7. 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/