IL-33 Promotes Food Anaphylaxis in Epicutaneously-Sensitized Mice By Targeting Mast Cells.
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
Claire Galand, PhD, Juan-Manuel Leyva-Castillo, PhD, Raif S. Geha, MD FAAAAI, Juhan Yoon, PhD, Michiko K. Oyoshi, PhD MSc FAAAAI, Alex Han, Andrew McKenzie, PhD, Michael Stassen
Rationale: Cutaneous exposure to food allergens predisposes to food allergy, which is commonly associated with atopic dermatitis (AD). The levels of the epithelial cytokine IL-33 are increased in skin lesions and serum of AD patients. Mast cells (MC) play a critical role in food anaphylaxis and express the IL-33 receptor ST2. The role of IL-33 in MC-dependent food anaphylaxis is unknown.We aim to determine the role and mechanism of action of IL-33 in food anaphylaxis in a model of IgE-dependent food anaphylaxis elicited by oral challenge of epicutaneously (EC)-sensitized mice. 

Methods: WT, ST2-deficient and MC-deficient KitW-sh/W-sh mice were EC sensitized with ovalbumin (OVA) then challenged orally with OVA. Body temperature was measured by telemetry, Il33 mRNA by qPCR, and IL-33, OVA-specific IgE and mouse mast cell protease 1 (mMCP-1) by ELISA. Bone marrow-derived MCs (BMMCs) degranulation was assessed by flow cytometry.

Results: Il33 mRNA expression was upregulated in tape-stripped mouse skin and scratched human skin, and tape stripping caused local and systemic IL-33 release in mice. ST2 deficiency, as well as ST2 blockade prior to oral challenge, significantly reduced the severity of oral anaphylaxis without affecting antigen-specific IgE or Th2 responses. Oral anaphylaxis was abrogated in KitW-sh/W-sh mice, and restored by reconstitution with WT, but not ST2-deficient, BMMCs. IL-33 significantly enhanced IgE-mediated degranulation of BMMCs in vitro.

Conclusions: IL-33 is released following mechanical skin injury, enhances IgE-mediated MC degranulation, and promotes oral anaphylaxis following EC sensitization by targeting MCs. IL-33 neutralization may be useful in treating food anaphylaxis in AD patients.