Loose lipid rafts lead to trigger-happy mast cells

Mast cells that accumulate cholesterol precursors in their membranes tend to overreact, according to Kovarova and colleagues on page 1161. This mast cell hyperresponsiveness might help explain why patients with a genetic disease known as Smith-Lemli-Opitz syndrome (SLOS) are prone to food allergies.

Patients with SLOS have abnormally low levels of circulating cholesterol—and a corresponding abundance of the cholesterol precursor 7-dehydrocholesterol (DHC)—due to defects in the gene that encodes the DHC-reducing enzyme (DHCR7). This cholesterol deficiency causes a bevy of developmental defects, consistent with the known requirement for cholesterol during embryonic development.

But the allergic manifestations of SLOS are poorly understood. Kovarova and colleagues suspected that mast cells—the principle allergy-triggering cell type—might be involved, as mast cells rely on the proper distribution of cholesterol-rich lipid rafts in their...