63 Pivotal Role of Intestinal Interleukin-17-Producing Gammadeltat Cells in the Food Allergy

BACKGROUND: Food allergy is a serious health problem, which affect 5% of children in westernized countries and evoke life-threatening hypersensitivity, termed anaphylaxis shock. Type 2 helper T cell (Th2) response and immunoglobulin E (IgE) has been implicated in the progression of food allergy, but the roles of specific lymphocyte subpopulations and cytokines remain to be clarified. METHODS: The mucosal adjuvant, cholera toxin (CT) and ovalbumin (OVA) were co-administered orally into mice, while OVA alone could induce oral tolerance. To evaluate the contribution of various cytokines, we used interleukin-17 (IL-17) or IL-23 knockout (KO) and wild type (WT) mice as control. RESULTS: Here we demonstrate that gamma delta T cells in the intestinal mucosa, as well as the cytokines interleukin-23 (IL-23) and IL-17, have pivotal roles to suppress the induction of serum OVA specific immunoglobulins and anaphylaxis in the food allergy model. The expression of IL-23, which was derived mostly from mucosal macrophages, and IL-17 levels were elevated after CT and OVA sensitization, and this induction of IL-17 was dependent on IL-23. CONCLUSIONS: These data, together with analysis of mice genetically disrupted for IL-17 and IL-23, suggest that IL-23 suppress the food allergy, whereas IL-17 has an important role in the anaphylaxis shock. Moreover, depletion of gamma delta T cells exacerbates the food allergy. We propose that T lymphocytes, including gamma delta T cells, could be a therapeutic target for mitigating the allergic response that evokes the anaphylaxis shock.