CXCR5, a G-protein coupled receptor, is the receptor for chemokine CXCL13. The CXCL13/CXCR5 axis is crucial in lymphoid neogenesis, lymphoid organization, and immune responses. This signaling axis is involved in multiple biological pathways and has overall biological importance in normal organism regulation as well as in the development of various diseases [1,2].

In a spinal nerve ligation (SNL) model of neuropathic pain, CXCR5 expression in spinal astrocytes was induced by SNL. Neuropathic pain was abrogated in Cxcr5-/-mice, indicating that CXCR5 expression was required for SNL-induced activation of spinal astrocytes and microglia. This shows the role of CXCR5 in the neuronal/astrocytic interaction in the spinal cord to facilitate neuropathic pain [3]. In a mouse model of sepsis-associated encephalopathy, CLP up-regulated CXCR5 in hippocampal microglia and impaired learning and memory. CXCR5 knockout enhanced autophagy and partially reversed cognitive deficits, suggesting that CXCR5 may contribute to cognitive dysfunction via the p38MAPK/NF-κB/STAT3 signaling pathway [4].

In conclusion, CXCR5 is essential in the regulation of immune responses and has a significant impact on various disease conditions. The use of Cxcr5 knockout mouse models has revealed its role in neuropathic pain and cognitive dysfunction associated with sepsis-associated encephalopathy, contributing to a better understanding of the underlying disease mechanisms.

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. Shen, Yanan, Zhang, Yuan, Du, Jiayue, Bao, Hongguang, Si, Yanna. 2021. CXCR5 down-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy: potential role of microglial autophagy and the p38MAPK/NF-κB/STAT3 signaling pathway. In Journal of neuroinflammation, 18, 246. doi:10.1186/s12974-021-02300-1. https://pubmed.ncbi.nlm.nih.gov/34711216/