Ever wonder why most people can eat peanuts or pasta without getting sick, while others have severe reactions? It turns out your immune system has to learn that food is safe — and a newly published study may explain how that learning happens, and what goes wrong when it doesn’t.
Researchers at the Weizmann Institute of Science have identified a cellular network responsible for oral tolerance, the process that teaches your immune system not to overreact to food. The study, published in Nature, may offer new clues about food allergies, celiac disease and other immune-related food sensitivities.
Oral tolerance starts before birth. Substances from the mother’s diet help train the developing immune system, and this process continues through breastfeeding and early exposure to solid foods. Helpful gut bacteria also play a role, teaching the body to accept many foreign substances as harmless.
For years, scientists believed this tolerance was managed by immune cells called dendritic cells. But in animal studies, even when these cells were removed, tolerance still developed. That led Dr. Ranit Kedmi and her team to look elsewhere.
Their breakthrough? A rare type of immune cell called ROR-gamma-t turned out to be the key player. When researchers blocked these cells from doing their job, mice quickly developed food allergies.
“Apparently, there is much more division of labor in the immune system than previously appreciated,” Kedmi explained. “Rather, completely different players — specific, rare cells — are dedicated to launching a mechanism that makes sure we can consume food safely.”
The team mapped a four-part cellular network that turns down the body’s defenses when food is present. This network works by silencing CD8 cells, which usually lead immune attacks. But the system is flexible: if the body detects a real infection, the “tolerance” program is paused so the immune system can fight off the threat — and resumes once the danger is gone.
This discovery could help researchers understand how food allergies and celiac disease develop when this system fails. It might even point to new ways to retrain the immune system in people with food sensitivities.
Kedmi’s research is supported by the Abisch-Frenkel RNA Therapeutics Center and the Gurwin Family Foundation.