A serious digestive disease appears to be connected to lymphatic function, scientists at the Oklahoma Medical Research Foundation have determined.
If confirmed through further research, the discovery by Sathish Srinivasan, Ph.D., and Xin Geng, Ph.D., could eventually lead to a new drug to treat or perhaps even prevent Crohn’s disease.
Crohn’s disease involves painful and sometimes debilitating inflammation of the digestive tract. According to the Crohn’s and Colitis Foundation, it affects about 1 in every 100 Americans and an estimated 6 million to 8 million people worldwide. It generally is diagnosed between adolescence and age 30.
Srinivasan and Geng study lymphatic vessels and valves, which help our bodies move fluids, prevent tissue swelling, fight infections and remove waste. Numerous disorders can result from improper development of lymphatic vessels and valves.
The OMRF researchers’ study provided clues on how lymphatic valves form. Using genetically engineered mice, they learned that when a particular gene known as S1PR1 is removed from the cells that line lymphatic vessels, fewer valves are made, and those that do form don’t function well. This was especially true of lymphatic valves in an area of the small intestine called the ileum.
“These mice had an excessive number of lymph node-like structures in the ileum,” said Geng. “This is similar to what people with Crohn’s disease experience.”
Srinivasan said it’s not clear whether excessive lymph-node-like structures cause Crohn’s disease or result from it, or whether those two things are unrelated.
“We have laid the groundwork to address that question, which would require testing of people with Crohn’s,” Srinivasan said. “Separately, we plan to collaborate with other labs to study the effects of S1PR1 in other organs.”
The Journal of Experimental Medicine published the new research, which was supported by grants Nos. R01HL131652, R01HL163095 and R01HL133216 from the National Heart, Lung, and Blood Institute and No. P20GM139763 from the National Institute of General Medical Sciences, both part of the National Institutes of Health. The project also received funding from the Oklahoma Center for Adult Stem Cell Research, a program of the Tobacco Settlement Endowment Trust.
