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

ABSTRACT Background IgE‐mediated food allergy is accompanied by mucosal mast cell (MMC) hyperplasia in the intestinal mucosa. Intestinal MMC numbers correlate with the severity of food allergy symptoms. However, the mechanisms by which MMCs proliferate excessively are poorly understood. Here, we clarify the role of newly identified MHC class II (MHCII)‐expressing MMCs in the effector phase of IgE‐mediated food allergy. Methods Mice reconstituted with MHCII‐deficient or wild‐type MMCs were used to generate a mouse mode of IgE‐mediated food allergy. We assessed the extent of intestinal MMC hyperplasia and the severity of hypothermia in these mice. In addition, we performed in vitro antigen presentation assay using induced MHCII‐expressing MMCs generated from bone marrow cells to evaluate the effect of CD4 + T cell activation on MMC proliferation. Results In food‐allergic mice, we identified the appearance of MHCII‐expressing MMCs in the intestinal mucosa and showed that MMC hyperplasia was suppressed in mice with MHCII‐deficient MMCs compared to mice with wild‐type MMCs. In vitro assays demonstrated that MHCII‐expressing MMCs incorporate food antigens directly and through the high‐affinity IgE receptor FcεRI‐mediated endocytosis and activate antigen‐specific CD4 + T cells from food‐allergic mice by antigen presentation. Activated CD4 + T cells secrete IL‐4 and large amounts of IL‐5, which enhance production of the mast cell growth factor IL‐9 by IL‐33‐activated MMCs. Excess IL‐9 causes excessive MMC proliferation, leading to the development of MMC hyperplasia. Conclusion Antigen presentation to CD4 + T cells by MHCII‐expressing MMCs triggers intestinal MMC hyperplasia and exacerbates IgE‐mediated food allergy.