Production of IL-12 by Peyer patch–dendritic cells is critical for the resistance to food allergy

BackgroundDendritic cells (DCs) play a pivotal role in antigen presentation and regulation of immune responses; however, their involvement in food allergy remains to be fully understood.ObjectiveOur aim was to investigate TH1-TH2 reciprocal regulation of DCs' function in the gut and systemic immune system and its effect on food allergy in mice with different susceptibility to food allergy.MethodsFreshly isolated CD11c+B220-DCs from peanut-sensitized allergy-susceptible C3H/HeJ and allergy-resistant Balb/c mice were cultured to determine levels of IL-12p70 produced in the presence of cytokines, including IL-4. Systemic levels of IL-12 were assessed in vivo after antigen challenge with or without IL-4. Targeted oral delivery of microencapsulated neutralizing anti–IL-12 antibody to Peyer patches (PPs) was performed in Balb/c before administration of each sensitizing dose.ResultsPeyer patch–DCs but not splenic DCs from sensitized C3H/HeJ but not Balb/c mice produced less IL-4–dependent IL-12p70. In vivo data confirmed this was restricted to the gut immune system, and it was not linked to reduced expression of IL-4 receptor or the lack of functional Toll-like receptor 4; instead, IL-4 failed to inhibit IL-10 production by PP-DCs, a pathway critically involved in IL-4–dependent production of IL-12p70. Finally, neutralization of IL-12 within PPs by specific antibody during antigen presentation significantly increased Balb/c susceptibility to food allergy.ConclusionReciprocal TH1-TH2 control of DCs' function within the inductive site of the gut immune system is altered in food allergy.Clinical implicationsProduction of IL-12p70 by PP-DCs during antigen presentation is critical for the development of food allergy.