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Why Late Nights Are Harmful to Your Immune System

Shift work, jet lag and even late nights staring at your smartphone or tablet might be making you sick. This is because the body’s internal clock is set for 12-hour periods of light and darkness. When the rhythm is thrown off, so will be your immune system. According to a new study, one of reasons for the above issue is that the genes that set the body clock are intimately linked to certain immune cells.

This finding was “a happy accident”, said Lora Hooper, an immunologist from the University of Texas Southwestern Medical Center at Dallas. She and co-workers were conducting research on NFIL3, a protein that can guide the development of certain immune cells and turn on activities of others. It is found that the gene for this protein is mutated in some human patients who suffer inflammatory bowel disease. In addition, the team found that in mice lacking the gene for NFIL3, there were more so-called TH17 cells in their intestines.

These cells are a kind of immune cells that are known as a T cell. Their name comes from a signal they produce, called interleukin 17, which informs other T cells to enhance the immune response.  At normal level, TH17 cells that live in the intestines can help the body fight against bacterial and fungal infections. However, when there are too many of them, the immune defense starts to cause illness instead of preventing it. The researchers also noted that boosting NFIL3 levels in T cells grown in lab could decrease the amount of them turning into TH17 cells, suggesting that the protein’s task is to prevent T cells from going into that area of specialization.  The researchers concluded that the absence of the protein would lead to runaway TH17 activity.

 Time is everything. When the body clock is disrupted, inflection-fighting TH17 cells in the intestine cause diseases. *Image source: Xiaofei Yu, Shipra Vaishnava and Yuhao Wang

At this point, the team had no reason to suspect a connection to the body’s internal timekeeping system—also known as circadian clock, which responds to daily light and dark cycles. However, as they further explored the connection between NFIL3 and TH17 cells, it was found that some of the proteins produced by the body’s “clock genes” attach to the NFIL3 genes. In addition, cultured cells and mice whose clock genes were tampered experimentally with generated fewer TH17 cells. Thus, the team surmise that one key protein in the clock network binds to the NFIL3 gene to maintain the production of TH17 cells in synchronization with periods of light and darkness. The researchers discovered that normal mice produce less NFIL3 and therefore more TH17 cells during the day than at night.

In the final experiment, the researchers applied jet lad on the mice. “We didn’t fly them anywhere,” Jokes Hooper. Instead, the researchers shifted the rodent’s light/dark cycles by 6 hours every 4 days. “It would be like flying from the States to Europe, India and Japan and spending 4 days in each country,” she explains. Comparing with mice having a normal day, mice with altered light cycles had nearly twice the amount of TH17 cells in their spleens and intestines and the team has reported these new findings online in Science. Those jet-lagged mice also mounted a stronger inflammatory response to experimental chemical-induced irritation—a test utilized to gauge immune-system sensitivity that hints the animals might be more prone to inflammatory disease.

These new findings add to a growing body of research showing that a healthy pattern of light and dark, sleeping and waking, is vital to maintain the immune system in perfect balance, says Hooper. She also notes that inflammation is the basis of a lot of chronic disorders like asthma, heart disease, chronic pain and many things ending in “-itis” such as dermatitis and bursitis. In developed countries, inflammatory conditions are more prevalent since people’s circadian rhythms are disrupted chronically. Even people who don’t have to work shifts or go across time zones still sleep and wake out of sync with light and darkness, says Hooper. “We all have screwed up light/dark cycles. We stay up late, keeps lights on, loot at our lit-up iPhones at 2 a.m.”

Immunologist Dan Littman at New York University finds the results in cultured cells convincing. He cautions, though, that the neatly defined pathway from clock gene to Th17 suppression may not be so tidy in living animals. “Even if NFIL3 is involved in the way they show, circadian disruption has influence on many other things.” He explains that stress hormones, gut bacteria and the actions of other types of T cells might also be taken into consideration for the effects of the experimental jet lag. Littman notes further that the increased inflammation in the jet-lagged animals was a response to an irritation induced by chemical, and more research should be done to prove a connection to inflammatory or autoimmune disease.

Hooper agrees that the current study is probably the tip of the iceberg and further research will yield deepening insight into the correlation between immune cells and circadian rhythms. She also hopes to work with other researchers to determine if TH17 cells are increased in humans with altered light/dark cycles chronically. For now, she tries to maintain her own sleeping patters more aligned with nature, starting by limiting exposure to artificial light at night. “I switch off the lights, I draw the curtains, and I keep my iPhone off.”

Source: News.sciencemag.org