BACKGROUND: Dendritic 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. OBJECTIVE: Our aim was to investigate T(H)1-T(H)2 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. METHODS: Freshly 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. RESULTS: Peyer 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. CONCLUSION: Reciprocal T(H)1-T(H)2 control of DCs' function within the inductive site of the gut immune system is altered in food allergy. CLINICAL IMPLICATIONS: Production of IL-12p70 by PP-DCs during antigen presentation is critical for the development of food allergy.
BACKGROUND: Dendritic 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. OBJECTIVE: Our aim was to investigate T(H)1-T(H)2 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. METHODS: Freshly 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. RESULTS: Peyer 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. CONCLUSION: Reciprocal T(H)1-T(H)2 control of DCs' function within the inductive site of the gut immune system is altered in food allergy. CLINICAL IMPLICATIONS: Production of IL-12p70 by PP-DCs during antigen presentation is critical for the development of food allergy.
Authors: Pierre Pochard; Brian Vickery; M Cecilia Berin; Alexander Grishin; Hugh A Sampson; Michael Caplan; Kim Bottomly Journal: J Allergy Clin Immunol Date: 2010-06-09 Impact factor: 10.793