18 April 2016
Food allergy is a major health issue, but its pathogenesis remains obscure. Group 2 innate lymphoid cells (ILC2) promote allergic inflammation. However their role in food allergy is largely unknown.
Food allergy-prone mice with a gain of function mutation in the IL-4 receptor a chain ( Il4raF709) were orally sensitized with food allergens and the ILC2 compartment was analyzed. The requirement for ILC2 in food allergy was investigated using Il4raF709, IL-33 receptor deficient ( Il1rl1 −/− ), IL-13 ( Il13 −/− ) and IL-4 ( Il4 −/− ) deficient mice and by adoptive transfers of in vitro-expanded ILC2. Direct effects of ILC2 on regulatory T (Treg) cells and mast cells were analyzed in co-culture experiments. Treg cell control of ILC2 was assessed in vitro and in vivo.
Food allergic Il4raF709 mice exhibit increased numbers of ILC2. IL-4 secretion by ILC2 contributes to the allergic response by reducing allergen-specific Treg cells and activating mast cells. IL-33 receptor deficiency in Il4raF709Il1rl1 −/− mice protects against allergen sensitization and anaphylaxis while reducing ILC2 induction. Adoptive transfer of WT and Il13 −/− but not Il4 −/− ILC2 restored sensitization in Il4raF709 Il1rl1 −/− mice. Treg cells suppress ILC2 in vitro and in vivo.
IL-4 production by ILC2 plays a crucial role in enabling sensitization to food allergens.