Immune system follows circadian clock

Mice with jet lag have boosted supply of cells linked to inflammation

UPSET CLOCK  Disrupting a mouse’s internal clock boosts the abundance of one type of immune cell, TH17 (false-colored green), in the lining of the intestines (gray fingerlike projections). The extra immune cells may make animals prone to inflammatory diseases.

Courtesy of Xiaofei Yu, Shipra Vaishnava and Yuhao Wang

Jet lag goofs up more than just sleep schedules: Tinkering with the body’s clock confuses the immune system too.

In mice, a type of immune cell linked to inflammation depends on daily cycles of light and dark, researchers report in the Nov. 8 Science. The finding could help explain the connection between inflammatory diseases and chronic clock disruptions, such as those experienced by frequent fliers and night shift workers.

“This has implications for all of us,” says study author Lora Hooper, an immunologist at the University of Texas Southwestern Medical Center in Dallas. “None of us go to sleep when the sun sets or get up when the sun rises.” Soaking up artificial light when it’s dark outside might predispose people to immune disorders such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, she says.

Humans, mice and virtually all other animals keep time with circadian clocks, internal clocks that sync up with the sun. A master clock in the brain uses light cues to set clocks throughout the body’s tissues. Researchers have tied people’s clocks to sleep patterns, metabolism and mood (SN: 4/10/10, p. 22).

Hooper’s team examined mice genetically engineered to lack a protein linked to both the circadian clock and to inflammatory bowel disease. The researchers noticed that the animals had inflamed intestines, speckled with more than the usual number of TH17 cells, a type of immune cell. These cells are usually the good guys, Hooper says. They help wipe out bacterial and fungal infections at body surfaces such as the skin and the lining of the gut and lungs.

But too many TH17 cells can stir up trouble. “It’s like if you get too many football fans together at the same time,” says Hooper. “They can riot.” When TH17 cells run amok, they trigger inflammation.

In the study, TH17 cells also piled up in normal mice’s intestines when researchers gave the animals chronic jet lag by repeatedly offsetting the animals’ light cycle by six hours. Compared with mice on regular schedules of light, the jet-lagged mice were more susceptible to inflammation triggered by a dose of chemicals.

Beyond TH17 cells, the immune system may have other players that march to the rhythm of a daily drum, says immunologist Dan Littman of New York University Langone Medical Center. “This is a new area of exploration,” he says. “The big picture is not quite there yet, but it’s certainly something important to follow up on.”

Meghan Rosen is a staff writer who reports on the life sciences for Science News. She earned a Ph.D. in biochemistry and molecular biology with an emphasis in biotechnology from the University of California, Davis, and later graduated from the science communication program at UC Santa Cruz.

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