S1pr4, a G protein-coupled receptor, is one of the five subtypes of sphingosine 1-phosphate receptors. Sphingosine 1-phosphate (S1P) binds to S1pr4, and this interaction is involved in regulating immune cell biology, including the trafficking of lymphocytes, neutrophils, and other cells. Signaling through S1pr4 is associated with multiple pathways, such as the NF-κB pathway, and is of great importance in immune-related biological processes and disease conditions [2].

In murine models, S1pr4-deficient mice showed reduced psoriasis severity, with attenuated production of CCL2, IL-6, and CXCL1, and a decrease in infiltrating monocytes and granulocytes, indicating its role in macrophage recruitment in psoriasis [1]. Ablation of S1pr4 in murine models of mammary and colitis-associated colorectal cancer delayed tumor development and improved therapy success through increased CD8+ T cell abundance, suggesting a tumor-promoting role of S1pr4 by restricting CD8+ T cell expansion [3]. In a murine asthma model, S1pr4 deficiency aggravated OVA/LPS-induced pulmonary inflammation with up-regulation in M1 macrophage activation, highlighting its potential as a therapeutic target for non-eosinophilic asthma [4].

In conclusion, S1pr4 plays crucial roles in immune-related biological processes. Gene-knockout mouse models have revealed its functions in diseases like psoriasis, cancer, and asthma. Understanding S1pr4 can provide new insights into the mechanisms of these diseases and potential therapeutic strategies.