When an enemy attacks, guards are moved to the location to neutralize the bandits. In the human body, a protein carrier called SPNS2 transports S1P molecules from endothelial cells to enhance immune cell responses in infected organs and tissues.

Using specially designed nanobodies that bind to SPNS2 and expand the entire structure, the expanded SPNS2 structure allows S1P molecules to be visualized by cryogenic electron microscopy. Scientists from the Immunology Translational Research Program at the Yong Lu Lin School of Medicine, National University of Singapore (NUS Medicine) and their partners at the Harbin Institute of Technology in China have analyzed the structure of the SPNS2 protein at an atomic level. provide greater insight into how S1P signaling molecules are released to interact with immune cells to regulate the inflammatory response.

“Seeing is believing. This work shows that SPNS2 is directly exporting S1P for signaling and that it is possible to inhibit its transport function with small molecules. This work is fundamental to understanding provides how S1P is released by SPNS2 and inhibits the function of this protein through small molecules for the treatment of inflammatory diseases,” said team leader Dr. Nguyen Nam Long.

The SPNS2 protein allows the binding of S1P signaling molecules to allow immune cells to leave the lymph nodes and cause inflammation in different parts of the body when needed. Made up of amino acids, the SPNS2 protein is weak enough to change its shape and structure to release S1P signaling molecules through small cavities found within the protein.

By discovering how the SPNS2 protein releases S1P molecules, the SPNS2 structure may be used for future drug development. Similar to discovering what a lock looks like before a key is designed, this discovery sheds more light on how future drugs can be better designed to enhance the protein’s efficacy. .

This finding builds on previous research that found that deletion of the SPNS2 protein from a preclinical model effectively blocks the S1P signaling pathway so that S1P signaling molecules do not immediately transport immune cells to leave the lymph node. can be done SPNS2 protein and S1P signaling molecules are essential for the recruitment of immune cells to inflamed organs, leading to the treatment of various inflammatory diseases.

“Using preclinical models, we have shown that targeting SPNS2 proteins in the body inhibits the inflammatory response in disease states, such as multiple sclerosis. This work allowed us to mimic this with small molecules. And has provided the possibility of inhibiting the function of pregnancy, which would go a long way toward treating inflammatory diseases more efficiently and effectively,” said Dr. Nguyen.