MHC Class II-Expressing Mucosal Mast Cells Promote Intestinal Mast Cell Hyperplasia in a Mouse Model of Food Allergy

Area of Science:

• Immunology
• Allergy Research
• Gastrointestinal Immunology

Background:

• IgE-mediated food allergy involves mucosal mast cell (MMC) hyperplasia in the gut.
• The mechanisms driving excessive MMC proliferation remain unclear.
• This study investigates the role of MHC class II (MHCII)-expressing MMCs in food allergy.

Purpose of the Study:

• To clarify the role of MHCII-expressing MMCs in the effector phase of IgE-mediated food allergy.
• To understand the mechanisms underlying MMC hyperplasia in food allergy.

Main Methods:

• Generated a mouse model of IgE-mediated food allergy using MHCII-deficient or wild-type MMCs.
• Assessed intestinal MMC hyperplasia and hypothermia severity.
• Performed in vitro antigen presentation assays to evaluate CD4+ T cell activation and its effect on MMC proliferation.

Main Results:

• Identified MHCII-expressing MMCs in food-allergic mouse intestinal mucosa.
• MMC hyperplasia was reduced in mice with MHCII-deficient MMCs.
• MHCII-expressing MMCs presented food antigens to CD4+ T cells, inducing IL-4, IL-5, and IL-9 production, which drives excessive MMC proliferation.

Conclusions:

• Antigen presentation by MHCII-expressing MMCs to CD4+ T cells triggers intestinal MMC hyperplasia.
• This process exacerbates IgE-mediated food allergy severity.