Food allergy in mice is modulated through the thymic stromal lymphopoietin pathway

Abstract

Background: Thymic stromal lymphopoietin (TSLP) is involved in the pathogenesis of allergic reactions in the skin and the lung. Nevertheless, data on the role of TSLP in food allergy are scarce. We explored the role of TSLP in a mouse model with oral sensitization and oral challenge eliciting food allergy. Methods: TSLP receptor (TSLPR)-/- mice and wild type mice were orally sensitized to β-lactoglobulin in presence of cholera toxin (CT) or CT alone. The elicited immune response was characterized in vitro and the mice were subsequently challenged with the antigen. Lymphocytes from various locations in the gut were activated either by the antigen or by CT and assayed for cytokine secretion. Results: Here we report that TSLPR-/- are less prone to generate food-induced reactions in conjunction with a decreased antigen-specific IgG1, but not IgE response. In addition, mesenteric lymphnode lymphocytes of TSLPR-/- mice were secreting lower quantities of IL-4, IL-5 and IL-10 after in vivo Ag activation, whereas higher numbers of IL-17 secreting cells were observed. Similarly, activation by the Th2-type adjuvant cholera toxin resulted in an increased frequency of IL-12 and IL-17 secreting lamina propria and mesenteric lymphocytes, together with increased production of IL-12 by activated dendritic cells in TSLPR-/- mice. Conclusions: TSLP can be considered as an essential, but not exclusive, mediator for elicitation of food allergy in mice, as well as a potential target for future therapeutic interventions.