Altered T Helper 17 Responses in Children with Food Allergy

Abstract

Background: While a central role for the T helper (Th) 1/Th2 axis in food allergy has been established, the Th17 response in food-allergic humans has not been addressed. Methods: Th17 responses in 18 peanut-allergic children, who were also allergic to at least one additional food allergen, were assessed relative to 15 age-matched healthy controls. To account for the atopy background in the allergic children, 7 atopic, but not food-allergic, individuals and their age-matched controls were included in this study. PBMCs were analyzed by flow cytometry ex vivo or were stimulated in vitro with peanut allergens, gliadin, or tetanus toxoid followed by analysis of proliferation and cytokine production in antigen-responsive cells. Results: We observed a significantly lower interleukin (IL) 17 production in CD4+ T cells of food-allergic individuals ex vivo (p < 0.02). In vitro, we found that IL-17 production in CD4+ T cells in response to all antigens tested was significantly impaired in food-allergic subjects compared to healthy controls (Ara: p < 0.005; gliadin: p < 0.004; TT: p < 0.03). No significant differences were observed between atopic and nonatopic individuals with no food allergy. Conclusion: Our results thus reveal a systemic, non-allergen-specific defect in Th17 responses to antigen stimulation in food allergic individuals, suggesting a role for Th17 cells in the control of food allergy and implicating IL-17 as a potential biomarker for tolerance to food antigens.

Gastrointestinal Immune Response to the Shrimp Allergen Tropomyosin: Histological and Immunological Analysis in an Animal Model of Shrimp Tropomyosin Hypersensitivity

“…Furthermore, these results are consistent with the higher level of Th2 cytokines, IL-4 and IL-6, and unaltered or lower levels of the Th1 cytokine, IFN-γ, in the intestinal mucosa of patients and mice with food allergy [11,38,50,51] . In light of our previous observation of IL-17 in this animal model and the significance of altered Th17 responses in food allergy [19,52] , future studies should be directed toward examining the contribution and interplay of Th1/Th2 as well as Th17 response in food allergies. Finally, because subjects who have outgrown their peanut allergy and those who are under potential treatment for allergies both exhibit a shifted Th1/Th2 cytokine profile, clearly further studies on cytokine profiles should be pursued [53][54][55][56][57] .…”

Increased production of IL-17 in children with autism spectrum disorders and co-morbid asthma

“…Thus, while we did not note increased levels of IL-17, IL-13, and IL-4 in ASD participants with food allergies compared to TD participants, we did observe that TD participants with food allergies produced higher levels of IL-17 compared to TD controls and ASD participants without food allergies. In a recent study of typically developing children with reported food allergies, the investigators found a higher production of IL-13 and IL-4 from in vitro isolated PBMC following a stimulation with a native peanut allergy mixture (Dhuban et al, 2013). While the T cell stimulation was directed towards a specific allergen rather than a pan-T cell mitogen, the cytokine profile was similar to what was noted in the current study for the typically developing children.…”

Years in Review: Recent Progress in Cellular Allergology

“…In support of this notion, Dhuban et al [34] found significantly lower IL-17 production by Th17 T cells derived from the peripheral blood of food-allergic individuals when compared to PBMCs of healthy controls. For that purpose, PBMCs were cultured with peanut allergen Ara h 1 or 2, gliadin or tetanus toxoid for 9 days.…”