Prevention of food allergy development and suppression of established food allergy by neutralization of TSLP, IL-25 and IL-33

Publication date: Available online 26 May 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Marat V. Khodoun, Sunil Tomar, Joel E. Tocker, Yui Hsi Wang, Fred D. Finkelman
BackgroundFood allergy (FA) is an increasing problem that has no approved treatment. The pro-Th2 cytokines, IL-25, IL-33 and TSLP, are associated with FA and monoclonal antibodies (mAbs) to these cytokines are reported to suppress murine FA development.ObjectiveDetermine whether anti-pro-Th2 cytokine mAbs can block both FA maintenance and induction.MethodsIgE-mediated FA was induced in BALB/c mice by oral gavage (o.g.) with medium chain triglycerides plus egg white (MCT/EW) and was characterized by increased numbers of lamina propria Th2 cells, mast cells shock, and eosinophils, shock (hypothermia), mast cell degranulation (increased serum MMCP1), increased serum IgG1 anti-EW and IgE, and increased IL-4 and IL-13 secretion following MCT/EW challenge. To suppress FA development, mice were injected with anti-IL-25, IL-33R, and/or TSLP monoclonal antibodies prior to the initial o. g. with MCT/EW; to suppress established FA, treatment with the same mAbs was initiated after FA development.ResultsInjection of a mAb to IL-25, IL-33R, or TSLP strongly inhibited FA development. No single mAb to a pro-Th2 cytokine could suppress established FA and optimal FA suppression required treatment with a cocktail of all three anti-pro-Th2 mAbs. Treatment with the three mAb cocktail during initial MCT/EW immunization induced EW tolerance.ConclusionAll of the pro-Th2 cytokines are required to induce our model of FA, while any pro-Th2 cytokine can maintain established FA. Pro-Th2 cytokines prevent oral tolerance. Combined treatment with antagonists to all three pro-Th2 cytokines or with an inhibitor of pro-Th2 cytokine production may be able to suppress established human FA.

Teaser

IL-25, IL-33 and TSLP are required to induce a mouse model of food allergy and all of these cytokines contribute to murine food allergy maintenance. This suggests an approach for suppressing human food allergy.


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