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Critical role of plasmacytoid dendritic cells in induction of oral tolerance.

Authors
  • Uto, Tomofumi1
  • Takagi, Hideaki1
  • Fukaya, Tomohiro1
  • Nasu, Junta2
  • Fukui, Takehito2
  • Miyanaga, Noriaki3
  • Arimura, Keiichi2
  • Nakamura, Takeshi3
  • Choijookhuu, Narantsog4
  • Hishikawa, Yoshitaka4
  • Sato, Katsuaki5
  • 1 Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; Japan Agency for Medical Research and Development (AMED), Tokyo, Japan. , (Japan)
  • 2 Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. , (Japan)
  • 3 Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. , (Japan)
  • 4 Division of Histochemistry and Cell Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. , (Japan)
  • 5 Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; Japan Agency for Medical Research and Development (AMED), Tokyo, Japan. Electronic address: [email protected] , (Japan)
Type
Published Article
Journal
The Journal of allergy and clinical immunology
Publication Date
Jun 01, 2018
Volume
141
Issue
6
Identifiers
DOI: 10.1016/j.jaci.2017.11.048
PMID: 29477579
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Exposure to dietary constituents through the mucosal surface of the gastrointestinal tract generates oral tolerance that prevents deleterious T cell-mediated immunity. Although oral tolerance is an active process that involves emergence of CD4+ forkhead box p3 (Foxp3)+ regulatory T (Treg) cells in gut-associated lymphoid tissues (GALTs) for suppression of effector T (Teff) cells, how antigen-presenting cells initiate this process remains unclear. We sought to determine the role of plasmacytoid dendritic cells (pDCs), which are known as unconventional antigen-presenting cells, in establishment of oral tolerance. GALT-associated pDCs in wild-type mice were examined for their ability to induce differentiation of CD4+ Teff cells and CD4+Foxp3+ Treg cells in vitro. Wild-type and pDC-ablated mice were fed oral antigen to compare their intestinal generation of CD4+Foxp3+ Treg cells and induction of oral tolerance to protect against Teff cell-mediated allergic inflammation. GALT-associated pDCs preferentially generate CD4+Foxp3+ Treg cells rather than CD4+ Teff cells, and such generation requires an autocrine loop of TGF-β for its robust production. A deficiency of pDCs abrogates antigen-specific de novo generation of CD4+Foxp3+ Treg cells occurring in GALT after antigenic feeding. Furthermore, the absence of pDCs impairs development of oral tolerance, which ameliorates the progression of delayed-type hypersensitivity and systemic anaphylaxis, as well as allergic asthma, accompanied by an enhanced antigen-specific CD4+ Teff cell response and antibody production. pDCs are required for establishing oral tolerance to prevent undesirable allergic responses, and they might serve a key role in maintaining gastrointestinal immune homeostasis. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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