Wiskott-Aldrich Syndrome (WAS) is a severe primary immunodeficiency that results from defects in WAS. In the Journal of Clinical Investigation, Fiebiger and colleagues shed light on the mechanistic basis of the atopy often seen in patients with WAS. These patients have elevated serum concentrations of IgE and food allergy. Was−/− mice show a similar manifestation of food allergy that is independent of the microbiota but is dependent on the adaptive immune system and the presence of food antigens. The absence of Was specifically in regulatory T cells (Treg cells) leads to (if anything) more-severe allergy and a strong type 2 immune-response signature, whereas allergic manifestations are not triggered by Was deficiency in dendritic cells or B cells. Was−/− Treg cells fail to suppress the TH2 subset of helper T cells and instead themselves acquire a TH2 cell–like phenotype. These data suggest that much of the allergic phenotype of patients with WAS results from defective Treg cell function.

J. Clin. Invest. (19 Sept 2016) 10.1172/JCI85129