Orally desensitized mast cells form a regulatory network with Treg cells for the control of food allergy
Yoshihiro Takasato, Yosuke Kurashima, Masahiro Kiuchi, Kiyoshi Hirahara, Sayuri Murasaki, Fujimi Arai, Kumi Izawa, Ayako Kaitani, Kaoru Shimada, Yukari Saito, Shota Toyoshima, Miho Nakamura, Kumiko Fujisawa, Yoshimichi Okayama, Jun Kunisawa, Masato Kubo, Naoki Takemura, Satoshi Uematsu, Shizuo Akira, Jiro Kitaura, Takao Takahashi, Toshinori Nakayama, Hiroshi Kiyono
Abstract
Oral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.