S1pr4, a member of the sphingosine-1-phosphate (S1P) G protein-coupled receptor family, has key functions in immune cell biology. It is involved in regulating cytokine production, immune cell trafficking, and differentiation, and is associated with pathways like NF-κB [1,2,3]. It plays an important role in multiple biological processes and diseases, making genetic models crucial for its study.

In a murine psoriasis model, S1pr4-deficient mice showed reduced psoriasis severity, with attenuated production of CCL2, IL-6, and CXCL1, and decreased infiltration of monocytes and granulocytes, indicating its role in regulating inflammatory responses [1]. In breast and colitis-associated colorectal cancer murine models, ablation of S1pr4 delayed tumor development and improved therapy success through increased CD8+ T cell abundance [4]. In asthma, S1pr4 deficiency aggravated OVA/LPS-induced pulmonary inflammation in mice along with up-regulation in M1 macrophage activation [5].

In conclusion, S1pr4 is essential in immune-related processes. KO/CKO mouse models have revealed its significance in diseases such as psoriasis, cancer, and asthma. These models help clarify its role in regulating inflammation, tumor growth, and immune cell activation, providing potential therapeutic targets for these diseases [1,4,5].

References:

1. Schuster, Christian, Huard, Arnaud, Sirait-Fischer, Evelyn, Brüne, Bernhard, Weigert, Andreas. 2020. S1PR4-dependent CCL2 production promotes macrophage recruitment in a murine psoriasis model. In European journal of immunology, 50, 839-845. doi:10.1002/eji.201948349. https://pubmed.ncbi.nlm.nih.gov/32017036/

2. Jozefczuk, E, Guzik, T J, Siedlinski, M. 2020. Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology. In Pharmacological research, 156, 104793. doi:10.1016/j.phrs.2020.104793. https://pubmed.ncbi.nlm.nih.gov/32278039/

3. Chen, Hongyu, Wang, Junmin, Zhang, Caiyun, Ji, Guang, Wu, Tao. 2022. Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 153, 113341. doi:10.1016/j.biopha.2022.113341. https://pubmed.ncbi.nlm.nih.gov/35785704/

4. Olesch, Catherine, Sirait-Fischer, Evelyn, Berkefeld, Matthias, Brüne, Bernhard, Weigert, Andreas. . S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion. In The Journal of clinical investigation, 130, 5461-5476. doi:10.1172/JCI136928. https://pubmed.ncbi.nlm.nih.gov/32663191/

5. Wang, Shanshan, Tian, Zhen, Lu, Yanjiao, Zhao, Jianping, Xie, Jungang. 2023. Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation. In International journal of biological sciences, 19, 1597-1615. doi:10.7150/ijbs.80256. https://pubmed.ncbi.nlm.nih.gov/37056936/