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 THI-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.

Production of IL-12 by Peyer patch-dendritic cells is critical for the resistance to food allergy / Temblay, Jeffrey N.; Bertelli, Eugenio; Arques, Juan L.; Regoli, Mari; Nicoletti, Claudio. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - ISSN 0091-6749. - STAMPA. - 120:(2007), pp. 659-665. [10.1016/j.jaci.2007.04.044]

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

NICOLETTI, CLAUDIO
2007

Abstract

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 THI-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.
2007
120
659
665
Temblay, Jeffrey N.; Bertelli, Eugenio; Arques, Juan L.; Regoli, Mari; Nicoletti, Claudio
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1093579
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