Ongoing inflammation and hyperresponsiveness of the lungs to allergens and pollutants is a key problem in asthma. In principle, the immune system has mechanisms to prevent such ongoing hyperresponsiveness, most importantly regulatory T cells. In asthma, immunosuppressive regulatory T cells become reprogrammed into pro-inflammatory TH2 and TH17 cells. Researchers at the Boston Children’s Hospital have demonstrated that the up-regulation of Notch4 receptor was critical to that switch. The Notch family of receptors is important for cell fate determination during development, and the authors concluded that “elucidating the respective roles of different Notch receptors in controlling disease outcome by modulating Treg cell responses may offer opportunities for precision medical interventions to restore immune tolerance in a tissue- and disease-specific manner.” Their work appeared in the Sept. 14, 2020, online issue of Nature Immunology.