Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance

Nat Immunol. 2016 May;17(5):545-55. doi: 10.1038/ni.3408. Epub 2016 Mar 28.


Oral tolerance prevents pathological inflammatory responses to innocuous foreign antigens by peripheral regulatory T cells (pT(reg) cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure for the 'instruction' of naive CD4(+) T cells to differentiate into pT(reg) cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs were dispensable, while classical dendritic cells (cDCs) were critical, for pT(reg) cell induction and oral tolerance. CD11b(-) cDCs from the gut-draining lymph nodes efficiently induced pT(reg) cells and, conversely, loss of transcription factor IRF8-dependent CD11b(-) cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in the induction of pT(reg) cells and their redundancy during the development of oral tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens / immunology*
  • CD11b Antigen / immunology
  • CD11b Antigen / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Diet
  • Flow Cytometry
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology*
  • Immunization / methods
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / immunology
  • Interferon Regulatory Factors / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology


  • Antigens
  • CD11b Antigen
  • Interferon Regulatory Factors
  • interferon regulatory factor-8

Associated data

  • GEO/GSE77305