Researchers at Johns Hopkins believe faulty TGF-beta signaling could be to blame for disrupting the way immune cells respond to common foods and environmental allergens.

Aberrant signaling by the protein called transforming growth factor-beta (TGF-beta) may be responsible for disrupting the way immune cells respond to common foods and environmental allergens, leading to a wide range of allergic disorders, according to study results. TGF-beta is known for its widespread effects in the body, from controlling how cells in a various organs grow and develop to overseeing how they communicate with one another.

For the study, investigators tracked 58 children with LDS with either a history of allergic disease or active allergies. The team homed in on a group of cells known as regulatory T-cells, which keep tabs on other immune cells to ensure that they don’t go into overdrive. Though LDS patients had unusually high levels of regulatory T-cells, the team noticed that — instead of acting in their regular role as inflammation tamers — the regulatory T-cells were secreting allergy-promoting signaling molecules called cytokines.

They also immersed undifferentiated, or naïve, immune cells from LDS patients in TGF-beta. The result: these “pre-specialized” cells quickly transformed into allergy-promoting immune cells known for their ability to recognize and attack pathogens, as well as otherwise innocent substances, like food proteins.

“Disruption in TGF-beta signaling does not simply nudge immune cells to misbehave but appears to singlehandedly unlock the very chain reaction that eventually leads to allergic disease,” said senior investigator Harry “Hal” Dietz, MD, a cardiologist at Johns Hopkins Children’s Center, professor in the McKusick-Nathans Institute of Genetic Medicine at Hopkins and director of the William S. Smilow Center for Marfan Research.