Role Change: Mast cells show an anti-inflammatory side

As anyone who has reacted to poison ivy can attest, the plant can induce maddeningly itchy skin. Researchers have now found that a cell once thought to be one of the chief perpetrators of this immune overreaction may actually keep the reaction from getting out of hand.

Mast cells make proteins that contribute to the inflammation that characterizes allergic reactions. The cells are part of the innate immune system, the frontline defense that rushes inflammatory cells and proteins to scenes of irritation or injury. Although mast cells play a valuable role in fighting bacteria and other pathogens, their conduct in allergic reactions appears rather like throwing gasoline on a fire.

A study in mice now shows that mast cells produce a helpful immune protein a few days after skin contact with urushiol, the key culprit in poison ivy and its partners in skin crime, poison oak and poison sumac. The protein, called interleukin-10, ratchets down the inflammatory reaction, says study coauthor Stephen J. Galli, a pathologist at Stanford University Medical Center.

Galli and his colleagues conducted a series of experiments using normal mice, mice whose mast cells were unable to produce interleukin-10, and mice lacking mast cells.

Rather than simply looking at skin reactions that appeared immediately after contact with urushiol, Galli’s colleague Michele A. Grimbaldeston decided to gauge the animals’ responses to urushiol several days later. By the third day, the mice lacking mast cells and those whose mast cells didn’t make interleukin-10 showed worse swelling and skin injury than did the normal mice.

As a backup test, the scientists repeated the experiments using an oft-studied chemical called 2,4-dinitro-fluorobenzene, which is known to cause allergic skin hypersensitivity. They found the same effect.

A third set of experiments showed that interleukin-10 made by mast cells also limited the kind of damage from chronic sun exposure that leads to skin wrinkling and predisposes a person to skin cancer.

The findings appear in the October Nature Immunology.

Various cells make interleukin-10. Some studies have suggested that its main sources are immune system “brakes” called regulatory T cells.

The new findings show that interleukin-10 “may be produced by different cells at different stages of an immune response,” says immunologist Anne O’Garra of the National Institute for Medical Research in London.

Mast cells’ long rap sheet had led some scientists to suggest that people might be better off without them. On the basis of the anti-inflammatory effect shown in this mouse study, however, Galli says, “you might want to think twice before eliminating this cell population.” Inducing mast cells to crank out copious interleukin-10 as needed would be beneficial, he says, but that would be a tall order.

Instead, researchers studying runaway immune reactions might now turn to asthma, in which mast cells have an inflammatory role. The new findings raise the question whether the cells might also limit airway inflammation during asthma attacks, says Galli.