How shifts in temperature prime immune response

Researchers at The Scripps Research Institute have found a temperature-sensing protein within immune cells that, when tripped, allows calcium to pour in and activate an immune response. This process can occur as temperature rises, such as during a fever, or when it falls-such as when immune cells are "called" from the body's warm interior to a site of injury on cooler skin.

The study, recently published online ahead of print by Nature Chemical Biology, is the first to find such a sensor in immune cells-specifically, in the T lymphocytes that play a central role in activation of killer immune cells. The protein, STIM1, previously known as an endoplasmic reticulum (ER) calcium sensor, had been thought to be important in immune function, and now the scientists show it is also a temperature sensor.

"Temperature has a profound effect on all biological processes including immune responses, but surprisingly little is known about molecules in immune cells that sense temperature sifts," said the study's principal investigator, Scripps Research Professor Ardem Patapoutian. "Here we show that STIM1 senses temperature and has a profound impact on immune cells."

This is the second family of thermosensation molecules that the Patapoutian laboratory has uncovered. The team has isolated and characterized three of six members of the transient receptor potential (TRP) family of ion channels-the so-called thermoTRPs. "These proteins translate temperature, which is a physical stimulus, into a chemical signal-ions flowing into cells," said Patapoutian. "ThermoTRPs mainly function in specialized sensory neurons that relay environmental temperature information to the brain."

In this study, the researchers turned to immune cells to look for temperature sensors. "Immune cells can experience dramatic temperature changes under either normal or pathophysiological conditions," said first author Bailong Xiao, a research associate in the Patapoutian laboratory. "The temperature drops significantly when, say, immune cells move from the 37 degree Celsius temperature of the spleen to skin, where it is normally 33 degrees. During fever, core body temperature can rise to 41 degrees." Scientists have discussed for decades whether fever is beneficial to the immune system. The researchers believe that identification of a molecular sensor of temperature within immune cells provides a novel avenue to address such questions mechanistically.

The research team, which included Bertrand Coste and Jayanti Mathur, also of the Patapoutian lab, found that STIM1 can be activated by heat with a high degree of temperature sensitivity. Both STIM1 and a plasma membrane pore-forming protein known as Orai1 have recently been identified as essential components of the so-called the calcium release activated calcium (CRAC) channel. But STIM1 had not been known to be heat sensitive until this research, according to Xiao.