IL-4 production by group 2 innate lymphoid cells promotes food allergy by
blocking regulatory T-cell function
#MMPMID27177780
Noval Rivas M
; Burton OT
; Oettgen HC
; Chatila T
J Allergy Clin Immunol
2016[Sep]; 138
(3
): 801-811.e9
PMID27177780
show ga
BACKGROUND: 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. OBJECTIVE: We sought to
investigate the role of ILC2s in food allergy. METHODS: Food allergy-prone mice
with a gain-of-function mutation in the IL-4 receptor ? chain (Il4raF709) were
orally sensitized with food allergens, and the ILC2 compartment was analyzed. The
requirement for ILC2s in food allergy was investigated by using Il4raF709, IL-33
receptor-deficient (Il1rl1(-/-)), IL-13-deficient (Il13(-/-)), and IL-4-deficient
(Il4(-/-)) mice and by adoptive transfer of in 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 assessed in vitro and
in vivo. RESULTS: Il4raF709 mice 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 in Il4raF709 Il1rl1(-/-) mice protects against allergen sensitization
and anaphylaxis while reducing ILC2 induction. Adoptive transfer of wild-type and
Il13(-/-) but not Il4(-/-) ILC2s restored sensitization in Il4raF709 Il1rl1(-/-)
mice. Treg cells suppress ILC2s in vitro and in vivo. CONCLUSION: 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.
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