CHICAGO, Oct. 7 (Xinhua) -- Researchers at Washington University School of Medicine in St. Louis have identified a type of immune cell known as type 3 innate lymphoid cells (ILC3) that are responsible for keeping the intestine operating in a normal, healthy manner.
By studying ILC3 taken from mouse intestines at six-hour intervals, the researchers found that the activity of clock genes varied in a predictable pattern over the course of a day, and that the activity of genes for immune molecules tracked with the clock genes.
When the researchers put some mice on a schedule similar to one experienced by a shift worker, an eight-hour change in the light-dark cycle every two days, the ILC3 cells no longer functioned normally. They produced low levels of immune molecules when stimulated to respond to an infection. Further, when mice were genetically modified to lack the clock protein REV-ERB alpha, the animals failed to develop normal quantities of ILC3 cells.
Using mice that lack the clock protein, as well as healthy mice for comparison, the researchers studied the effect of infection with the bacterium Clostridium difficile, which can cause severe diarrhea in people. The mice without the clock protein failed to mount an effective defense: Their ILC3 cells produced more of a damaging immune molecule and less of a protective immune molecule, and the bacteria spread more widely in their bodies.
ILC3 cells maintain equilibrium in the gut by fortifying the barrier between the trillions of bacteria that normally live inside the gut and the cells that make up the intestine itself. They also produce immune molecules that help the gut's immune system avoid overreacting to harmless microbes and food particles, while preserving its ability to combat disease-causing micro-organisms.
This suggests that targeting clock genes could affect immune cells and help counter the negative effects of erratic sleep schedules associated with intestinal illnesses.
The researchers will continue to study the role of circadian rhythms on the digestive tract.
The findings were published on Friday in Science Immunology.
