Jet lag, shift work, and even late nights staring at your tablet or smartphone may be making you sick. That's because the body's internal clock is set for two 12-hour periods of light and darkness, and when this rhythm is thrown off, so is the immune system. One reason may be that the genes that set the body clock are intimately connected to certain immune cells, according to a new study.

The finding “was a happy accident," says Lora Hooper, an immunologist at the University of Texas Southwestern Medical Center in Dallas. She and her colleagues were studying NFIL3, a protein that guides the development of certain immune cells and turns on the activity of others. The gene for this protein is mutated in some human patients with inflammatory bowel disease, and mice lacking the gene for NFIL3, the team found, had more so-called TH17 cells in their intestines.

These cells are a type of immune cell known as a T cell. They get their name from a signal they produce, called interleukin 17, which tells other T cells to increase the immune response. In normal numbers, TH17 cells, which live in the intestines, help the body fight bacterial and fungal infections. But when there are too many, the immune defense begins to cause illness rather than prevent it. Boosting NFIL3 levels in T cells growing in lab cultures resulted in fewer of them turning into TH17 cells, the researchers found, suggesting that the protein's job is to prevent T cells from going into that area of specialization. The absence of the protein, the team concluded, leads to runaway TH17 activity.

At this point, the researchers had no reason to suspect a connection to our body’s internal timekeeping system—also known as our circadian clock—which responds to daily cycles of light and dark. But as they continued to explore the connection between NFIL3 and TH17 cells, they found that some of the proteins produced by the body’s "clock genes” attach to the NFIL3 genes. What's more, cultured cells and mice whose clock genes were experimentally tampered with produced fewer TH17 cells. The researchers surmise that a key protein in the clock network binds to the NFIL3 gene to keep the production of TH17 cells synchronized with periods of light and darkness. And the team found that normal mice produce less NFIL3, and thus more TH17 cells, during the day than at night.

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 reports online today 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, and many things ending in "-itis," like 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 in New York City 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.

Littman also notes that the increased inflammation in the jet-lagged animals was a response to an induced chemical irritation, and more research is needed to prove a link to inflammatory or autoimmune disease.

Hooper agrees that the present study is probably the tip of the iceberg, and more research will yield deepening insight into the relationship between immune cells circadian rhythms. She is hoping to collaborate with other researchers to determine if TH17 cells are increased in humans with chronically altered light cycles. For now, she says, she tries to keep her own sleeping patterns more aligned with nature, starting by limiting exposure to artificial light at night. "I turn off the lights, I draw the curtains, and I keep my iPhone off."

ScienceNOW, the daily online news service of the journal Science

Also on HuffPost:

Loading Slideshow...
  • Myth: Everyone Needs Eight Hours Of Sleep A Night

    <strong>Fact: </strong>What works for you might not work for your neighbor. "A person's sleep need is genetically pre-determined," says Michael Decker, Ph.D., associated professor at Georgia State University and spokesperson for the American Academy of Sleep Medicine. "Some people need a little bit more, and some need a little bit less." So how do you know how much you need? One tell-tale sign you're not getting enough is falling asleep as soon as you get into bed, says Robert Oexman, D.C., director of the <a href="http://www.sleeptolive.com/" target="_blank">Sleep to Live Institute</a>. "It's very common that people tell me, 'I'm a great sleeper, I fall asleep as soon as my head hits the pillow,'" he says. "That's a sign that you're probably not getting enough sleep." Drifting off should take around 15 minutes if you're regularly fulfilling your sleep needs, he says. And if you wake up feeling refreshed and energetic? You're doing something right, says Decker. However, the people who say they're fine with just six hours of sleep a night are likely setting themselves up for future problems. Research suggests that consistently sleeping fewer than six hours a night can increase stroke and diabetes risk, damage bones and hurt the heart, among other <a href="http://www.huffingtonpost.com/2013/03/06/scary-sleep-deprivation-effects_n_2807026.html" target="_blank">scary side effects</a>.

  • Myth: If You Can Get It, More Sleep Is Always Better

    <strong>Fact:</strong> There is such a thing as <em>too much</em> sleep, believe it or not. Just like people who regularly sleep fewer than six hours a night, people who consistently clock more than nine or 10 hours a night also face a number of health problems, says Michael A. Grandner, Ph.D., an instructor of psychiatry and a member of the Behavioral Sleep Medicine program at the University of Pennsylvania. We don't quite know yet if too much sleep is the proverbial chicken or the egg, he says, but we do know there is such a thing as too much of a good thing.

  • Myth: You Can Make Up For Lost Sleep By Sleeping In On The Weekends

    <strong>Fact:</strong> If you're grouchy and crabby from skimping on sleep all week, and then sleep a couple extra hours Saturday morning, you'll find the short-term effects of sleep deprivation vanish pretty quickly, says Grandner. But the long-term impact is still likely dangerous. "The problem [with counting on catching up on sleep] is thinking there's <em>not</em> a consequence of not getting enough sleep all week," says Oexman. "There are consequences of even one night of not getting enough sleep." Plus, if you sleep in <em>too</em> late on the weekends, you're setting yourself up for trouble falling asleep Sunday night. Then, when the alarm goes off Monday morning, you'll find yourself starting the cycle all over again, says Oexman.

  • Myth: If You Can't Sleep, Just Rest In Bed

    <strong>Fact:</strong> Turns out, lying there staring at the clock hoping sleep will come is one of the <em>worst</em> things you can do, the experts say. "Lying in bed and ruminating about why we're not sleeping can increase anxiety and make it harder to fall asleep," says Decker. If you stew there long enough, you may teach your brain to associate lying in bed with being awake, says Oexman. Instead, get out of bed and do something else for a while to help you wind down. The change of environment can help you avoid a stressful association with your bedroom, as long as it's nothing too exciting and away from any bright light. Half an hour later, try getting back into bed, says Grandner.

  • Myth: Watching TV Is A Good Way To Relax Before Bed

    <strong>Fact: </strong>"There's a difference between relaxation and distraction," says Grandner. When you relax, your breathing and heart rate slow down, your muscles release, your thoughts grow calmer -- and none of that happens when you're watching TV. "TV at night is not there to help you sleep, it is there to sell you stuff," he says. Not to mention that the blue light emitted from the TV tricks your brain into thinking it's time to be awake and alert. Experts agree that you should power down all electronic devices at least an hour before bed. Reading a book (that isn't too exciting) can help you relax, but sleep docs are quick to point it has to be the real thing. iPads and other backlit electronic readers emit the same kind of stimulating light as your TV.

  • Myth: Snoring Is Annoying, But Mostly Harmless

    <strong>Fact:</strong> While certainly a nuisance to your bedmate, snoring can be more dangerous to your health than you might know. The vibrations of the soft tissue of your airways that leads to that log-sawing sound can cause swelling overtime. As the swelling further narrows your airways, it becomes increasingly difficult for enough oxygen to pass through, says Oexman. When it's not getting enough oxygen, the brain will trigger snorers to wake up, says Grandner. Most people who snore or have sleep apnea almost immediately fall back to sleep, but some experts hypothesize that the constantly cycling between alert and asleep causes a great deal of stress in the body, particularly to the heart, says Grandner. This could explain why <a href="http://www.huffingtonpost.com/dr-michael-j-breus/snoring-health-risk_b_2743494.html" target="_blank">both snoring and sleep apnea have been linked to increased heart risks</a>.

  • Myth: Alcohol Will Help You Sleep

    <strong>Fact:</strong> It might help you doze off, but it becomes seriously detrimental to the quality of your shut-eye later on in the night. It's a much more complicated relationship than just "alcohol makes you pass out," says Grandner. As your body processes the alcohol, it can begin to act as a stimulant, leading to more shallow and less restful sleep later in the night. Drinkers may also be more likely to wake up in the middle of the night and have trouble falling back to sleep. "Alcohol is very disruptive to sleep continuity and leads to fragmented sleep and poor sleep quality," says Decker. "Drink now, pay later."

  • Myth: An Afternoon Coffee Won't Affect Your Sleep

    <strong>Fact:</strong> Caffeine has a surprisingly-long half life, meaning there's still about half of the original amount of caffeine you ingested in your blood about <em>12 hours later</em>, says Oexman. Caffeine isn't always the most obvious of sleep-stealers, however. "In most cases when it comes time to sleep, you just don't quite feel ready for it," says Grandner. "You're not feeling the caffeine jitters, you're just less able to wind down, even if you don't realize that it could be a culprit." Even lunchtime caffeine could cause trouble if you're particularly sensitive to caffeine, but definitely steer clear of any after-dinner coffee or tea.

  • Myth: Your Bedroom Should Be Warm And Cozy

    <strong>Fact:</strong> Even though we totally understand the urge to cuddle up under loads of blankets, a cooler environment is more conducive to good sleep. Because there are specific changes in core body temperature as we prepare for sleep, anything that raises your internal temp can make sleep more difficult, says Grandner. Some people would rather save on electricity and turn the AC off at night, but if you find yourself struggling to sleep as the weather warms up, try keeping a fan running at least, he suggests. In most cases, says Oexman, having your head exposed to some cool air will counteract the effects of too many blankets, but for <a href="http://www.huffingtonpost.com/2012/02/14/sleep-compatibility-_n_1274860.html" target="_blank">bedmates with opposite temperature needs</a>, he suggests sleeping with two sets of sheets and blankets, even if you're in the same bed.

  • Myth: Taking A Nap Will Mess With Your Sleep At Night

    <strong>Fact:</strong> When timed right, it shouldn't! In fact, there's substantial research that shows <a href="http://www.huffingtonpost.com/2013/03/11/nap-benefits-national-napping-day_n_2830952.html" target="_blank">nappers have improved memory</a>, alertness and performance after a short siesta. Make sure you're not napping too close to bedtime, and cut it to <a href="http://www.huffingtonpost.com/2012/01/26/how-to-nap-at-work_n_1232352.html" target="_blank">30 minutes or less</a>, otherwise you risk drifting into deeper sleep and feeling groggier when you wake up. A word of caution for people who have difficulty sleeping: If you already find it hard to fall asleep, wake up multiple times throughout the night or wake up too early, it's probably wise to skip the nap, says Oexman.

  • Myth: Exercising At Night Will Keep You Awake

    <strong>Fact: </strong>Not necessarily. This thinking probably stems from studies of people doing much more intense exercise much closer to bedtime than most of us really do, says Grandner. If you have no other time than at night to hit the gym, don't skip the workout, just make sure it isn't <em>too</em> rigorous and that you allow yourself ample time to cool off before jumping into bed, says Grandner. However, if you already have trouble falling asleep at night, the boost to our core body temperature caused by exercise could add fuel to the fire, says Oexman. People with trouble sleeping should look to exercise at least three to four hours before bedtime, he says.

  • Myth: It's OK For Your Pet To Share Your Bed

    <strong>Fact:</strong> Your furry friends are not the best bed partners. "Some people feel that having their pet in the room helps them sleep better," says Decker, "but if Fido snores and Fluffy is roaming around on the bed as cats often do, it can be very disruptive!"

FOLLOW SCIENCE