2018/08/01
Kyushu University
Keio University
Japan Agency for Medical Research and Development
A research group from the Medical Institute of Bioregulation at Kyushu University, led by Principal Investigator Yoshinori Fukui, Associate Professor Taketo Uruno, and Tetsuya Sakurai, a third-year student in the Doctoral Programs, in collaboration with a research group from the Keio University School of Medicine led by Lecturer Yuki Sugiura and Guest Professor Makoto Suematsu, has made a world-first discovery. They found that a lipid called cholesterol sulfate, contained in tears, inhibits the function of a protein called DOCK2, which is important for the movement of immune cells, thereby protecting the eye from the infiltration of inflammatory cells.
The immune system is an essential defense system that has evolved to protect the body by promptly eliminating foreign substances such as pathogenic microorganisms. However, excessive immune responses carry the risk of also attacking normal tissues. For this reason, there are tissues and spaces in the body where the immune surveillance mechanism is less likely to be activated, known as "immune-privileged sites." The eye is one such site, and while several proteins have been reported to be involved in immune evasion, the role of bioactive lipids has remained unclear. The research group focused on DOCK2, a molecule essential for immune cell motility. In the process of searching for its inhibitors, they discovered that cholesterol sulfate strongly suppresses the function of DOCK2 and stops the movement of immune cells. Detailed analysis using mice revealed that cholesterol sulfate is produced in large quantities in the Harderian gland (equivalent to the human meibomian gland), a tissue that supplies lipid components to tears, and indeed, large amounts of cholesterol sulfate were found in tears. In genetically modified mice unable to produce cholesterol sulfate, eye inflammation accompanied by immune cell infiltration was exacerbated by UV irradiation or antigen administration. On the other hand, this inflammation was suppressed by applying cholesterol sulfate eye drops. These findings suggest that cholesterol sulfate is a promising target molecule for artificially conferring or revoking immune privilege.
This research is a result of the LEAP (Incubate Type) program of the Innovative Advanced Research and Development Support Project by the Japan Agency for Medical Research and Development (AMED), and will be published in the American scientific journal "Science Signaling" at 2:00 p.m. on Tuesday, July 31, 2018 (U.S. Eastern Daylight Time).
For the full press release, please see below.