The spleen is the site where mast cells are induced in the development of food allergy

Int Immunol. 2017 Jan 1;29(1):31-45. doi: 10.1093/intimm/dxx005.

Abstract

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.

Keywords: T cells; food allergy; mast cell; spleen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Food Hypersensitivity / immunology*
  • Food Hypersensitivity / pathology
  • Interferon-gamma / immunology
  • Interleukin-3 / immunology
  • Mast Cells / immunology*
  • Mast Cells / pathology
  • Mice
  • Mice, Inbred BALB C
  • Spleen / immunology*
  • Spleen / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology

Substances

  • IFNG protein, mouse
  • Interleukin-3
  • Interferon-gamma