IL-4 production by group 2 innate lymphoid cells promotes food allergy by blocking regulatory T-cell function

    loading  Checking for direct PDF access through Ovid



Food allergy is a major health issue, but its pathogenesis remains obscure. Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation. However their role in food allergy is largely unknown.


We sought to investigate the role of ILC2s in food allergy.


Food allergy–prone mice with a gain-of-function mutation in the IL-4 receptor α chain(Il4raF709)were orally sensitized with food allergens, and the ILC2 compartment was analyzed. The requirement for ILC2s in food allergy was investigated by usingIl4raF709, IL-33 receptor–deficient(Il1rl1−/−), IL-13–deficient(Il13−/−), and IL-4–deficient(Il4−/−)mice and by adoptive transfer ofin vitro–expanded ILC2s. Direct effects of ILC2s on regulatory T (Treg) cells and mast cells were analyzed in coculture experiments. Treg cell control of ILC2s was assessedin vitroandin vivo.


Il4raF709mice with food allergy exhibit increased numbers of ILC2s. IL-4 secretion by ILC2s contributes to the allergic response by reducing allergen-specific Treg cell and activating mast cell counts. IL-33 receptor deficiency inIl4raF709 Il1rl1−/−mice protects against allergen sensitization and anaphylaxis while reducing ILC2 induction. Adoptive transfer of wild-typeand Il13−/−but notIl4−/−ILC2s restored sensitization inIl4raF709 Il1rl1−/−mice. Treg cells suppress ILC2sin vitroandin vivo.


IL-4 production by IL-33–stimulated ILC2s blocks the generation of allergen-specific Treg cells and favors food allergy. Strategies to block ILC2 activation or the IL-33/IL-33 receptor pathway can lead to innovative therapies in the treatment of food allergy.

Related Topics

    loading  Loading Related Articles