The spleen is the site where mast cells are induced in the development of food allergy.
It has been reported that splenic immune responses play pivotal roles in the development of allergic diseases; however, the precise role of the spleen remains unclear. Herein, we demonstrated a novel role of the spleen in the pathogenesis of food allergy (FA). We found that mast cells (MCs) developed from progenitor cells present in spleen during an antigen-specific T-cell response in vitro. In a Th2 response-mediated FA model, significant expansion of MCs was also observed in spleen. The incidence of allergic diarrhea was profoundly reduced in splenectomized mice, whereas adoptive transfer of in vitro-induced splenic MCs into these mice restored allergic symptoms, suggesting that the splenic MCs functioned as the pathogenic cells in the development of FA. The in vitro-generated MCs required not only IL-3 but also IFN-γ, and treatment of FA-induced mice with anti-IFN-γ antibody suppressed expansion of MCs in spleen as well as diarrhea development, highlighting that IFN-γ in the spleen orchestrated the development of FA, which was followed by a Th2 response in the local lesion. Overall, we propose that the role of the spleen in the development of FA is to provide a unique site where antigen-specific T cells induce development of pathogenic MCs.
Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.|Allergy and Immunology Project Group, Research Institute of Medical Science, Center for Institutional Research and Medical Education, Nihon University School of Medicine, Itabashi-Ku, Tokyo 173-8610, Japan.
Shota
S
Toyoshima
Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.
Ei
E
Wakamatsu
Department of Pathology, Teikyo University Chiba Medical Center, Ichihara, Chiba 299-0111, Japan.
Yasuo
Y
Ishida
Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.
Yuuki
Y
Obata
Division of Mucosal Immunology, Department of Microbiology and Immunology.|International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.|Department of Innovative Medicine, Graduate School of Medicine.|Institute for Global Prominent Research.|Departments of Mucosal Immunology and Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Yosuke
Y
Kurashima
Division of Mucosal Immunology, Department of Microbiology and Immunology.|International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.|Departments of Mucosal Immunology and Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Hiroshi
H
Kiyono
Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.
Ryo
R
Abe
D000818:Animals; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000276:immunology; D007377:Interleukin-3 / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
C000611649:IFNG protein, mouse; D007377:Interleukin-3; D007371:Interferon-gamma
T cells; food allergy; mast cell; spleen