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


CONCLUSIONS
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.


CONCLUSIONS
Production of IL-12p70 by PP-DCs during antigen presentation is critical for the development of food allergy.
Temblay
Jeffrey N
JN
Gastrointestinal Biology and Health Program, Institute of Food Research, Norwich, United Kingdom.
Bertelli
Eugenio
E
Arques
Juan L
JL
Regoli
Mari
M
Nicoletti
Claudio
C
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005512:Food Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E