The immune system is an essential defense system that has evolved to quickly eliminate foreign substances such as pathogenic microorganisms and protect living organisms, but an excessive immune response carries the risk of attacking normal tissues as well.For this reason, there are tissues and spaces in the living body where the immune monitoring mechanism is difficult to activate, and these are called "immune privileged sites".The eye is one of them, and it has been reported that several proteins act on immune avoidance, but the role of bioactive lipids has not been clarified.

　The research group focused on a protein called DOCK2, which is an essential molecule for immune cells to move, and in the process of searching for its inhibitor, a lipid called cholesterol sulfate strongly suppresses the action of DOCK2 and stops the movement of immune cells. I found that.As a result of detailed analysis using mice, cholesterol sulfate is produced in large quantities in the Harder gland (corresponding to the human meibomian gland), which is the tissue that supplies the lipid component to tears, and in fact, it is contained in tears. It contained a large amount of cholesterol sulfate.In mice genetically engineered to prevent the production of cholesterol sulfate, UV irradiation and antigen administration exacerbated eye inflammation associated with immune cell infiltration.On the other hand, this inflammation was suppressed by instillation of cholesterol sulfate.

　Based on the results of this research, cholesterol sulfate is expected to be a good target molecule for developing a method for artificially imparting or depriving immune privilege.

Paper information:[Science Signaling] Cholesterol sulfate is a DOCK2 inhibitor that mediates tissue-specific immune evasion in the eye