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.