In a final experiment, the researchers gave the mice jet lag. "We didn't fly them anywhere," Hooper jokes. Instead, the team shifted the rodents' light/dark cycles by 6 hours every 4 days. "It would be like flying from the U.S. to Europe, India, and Japan and spending 4 days in each country," she explains. Mice with altered light cycles had nearly twice as many TH17 cells in their spleens and intestines, compared with mice having a normal day, the team reported online Wednesday in Science. The jet-lagged mice also mounted a stronger inflammatory response to irritation by an experimental chemical — a test used to gauge immune-system sensitivity that hints the animals may be more prone to inflammatory disease.
The finding adds to a growing body of research showing that a healthy pattern of light and dark, sleeping and waking, is essential to keep the immune system in balance, Hooper says. She notes that inflammation is the basis of many chronic disorders, such as heart disease, asthma, chronic pain, bursitis and dermatitis. Inflammatory conditions are more prevalent in developed countries, where people's circadian rhythms are chronically disrupted. Even people who don't work shifts or cross time zones still wake and sleep out of sync with light and darkness, Hooper says. "We all have screwed up light cycles. We stay up late, keep the lights on, look at our lit-up iPhones at 2 a.m."
Immunologist Dan Littman of New York University finds the results in cultured cells convincing. He cautions, though, that the neatly defined pathway from clock gene to TH17 suppression might not be so tidy in a living animal. "Even if NFIL3 is involved in the way they show, circadian disruption affects many other things." Stress hormones, gut bacteria, and the actions of other types of T cells may also account for the effects of the experimental jet lag, he says.