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

Christophe P Frossard,Simone C Zimmerli,Philippe A Eigenmann,José M Rincon Garriz

doi:10.1186/s13601-016-0090-2

Abstract

BackgroundThymic 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.MethodsTSLP 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.ResultsHere 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.ConclusionsTSLP 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.

Highlights

Thymic stromal lymphopoietin (TSLP) is involved in the pathogenesis of allergic reactions in the skin and the lung
Assessment of TSLP receptor (TSLPR)−/− mice at the same time points showed predominantly mild or no symptoms of anaphylaxis (Fig. 1b) and a faster recovery correlating to only a slight decrease in body temperature
These results suggest that food-mediated allergic reactions are, to a significant extent, mediated by a TSLP-dependent mechanism

Summary

Introduction

Thymic stromal lymphopoietin (TSLP) is involved in the pathogenesis of allergic reactions in the skin and the lung. The pathogenesis of food allergy involves various mechanisms, all closely associated with the gut-related immune system [1]. Mice models of food allergy with oral sensitization to common food antigens eliciting anaphylactic reactions upon re-exposure have allowed extensive description of Th2-type, gutrelated mechanisms of IgE-mediated food allergy [2, 3]. TSLP has a close four helix structural analogy to IL-7, and can be found secreted in increased amounts in epithelial cells (EC) of the skin, the lung and the gut. TSLP receptor (TSLPR)−/− mice lacking responsiveness to TSLP fail to express Th2-type cytokines and lung inflammation [15, 16]. Intestinal EC produce TSLP, and expression of TSLP and the TSLPR are closely linked to inflammation mediated by IL-12, IL-17, and Th2-type cytokines [18, 19]

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