Circadian rhythms influence immune function

Most organisms on Earth exhibit circadian rhythms – variations in cellular activity that oscillate with the day-night cycle. It is recognised that the circadian clock controls processes such as sleep and metabolism, but scientists have recently shown that it may also have a role in regulating the immune system.

A team from the UT Southwestern Medical Center demonstrated that production of a type of white blood cell, known as Th17 cells, fluctuates according to the light-dark cycle. Th17 cells are a kind of T-lymphocyte, named because they produce a molecule called IL-17. They protect us from bacteria and fungi at mucosal surfaces, such as in the gut, but over-activity has been implicated in autoimmunity. Development of a T cell into a Th17 cell is directed by a protein called RORγt.

Expression of a protein called NFIL3 is controlled by the circadian clock so its concentration is lower during the day than at night. The researchers found that NFIL3 in turn regulates expression of RORγt, inhibiting its production. They showed that increasing the amount of NFIL3 in T cells reduces RORγt expression and prevents the cells from developing into Th17 cells. Since Th17 cells live for a relatively long time, the scientists saw no variation in the Th17 cell population in the guts of mice over 24 hours, but by disrupting the mice’s light-dark cycle so that it was always light, they showed that Th17 cell numbers in the guts of these mice increased compared to mice subjected to normal light-dark cycles.

In our modern lives we often experience day-night cycle disruptions; for example night work and long-haul flights. Such perturbations are associated with increased incidence of inflammatory diseases. This study is exciting because it reveals a new pathway that could potentially be manipulated to enhance or dampen the immune response.

Read more at: http://www.utsouthwestern.edu/newsroom/news-releases/year-2013/nov/immune-clock-hooper.html