In vivo induction of Tr1 cells via mucosal dendritic cells and AHR signaling

PLoS One. 2011;6(8):e23618. doi: 10.1371/journal.pone.0023618. Epub 2011 Aug 23.


Background: Type 1 regulatory T (Tr1) cells, characterized by the secretion of high levels of the anti-inflammatory cytokine interleukin-10 (IL-10), play an important role in the regulation of autoimmune diseases and transplantation. However, effective strategies that specifically induce Tr1 cells in vivo are limited. Furthermore, the pathways controlling the induction of these cells in vivo are not well understood.

Methodology/principal findings: Here we report that nasal administration of anti-CD3 antibody induces suppressive Tr1 cells in mice. The in vivo induction of Tr1 cells by nasal anti-CD3 is dependent on IL-27 produced by upper airway resident dendritic cells (DCs), and is controlled by the transcription factors aryl hydrocarbon receptor (AHR) and c-Maf. Subsequently, IL-21 acts in an autocrine fashion to expand and maintain the Tr1 cells induced in vivo by nasally administered anti-CD3.

Conclusions/significance: Our findings identify a unique approach to generate Tr1 cells in vivo and provide insights into the mechanisms by which these cells are induced.

Publication types

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

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies / administration & dosage
  • Antibodies / pharmacology
  • Autoimmunity / drug effects
  • CD3 Complex / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Interleukin-17 / metabolism
  • Interleukins / metabolism
  • Mice
  • Models, Immunological
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / immunology*
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Receptors, Interleukin-21 / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / metabolism


  • Antibodies
  • CD3 Complex
  • Interleukin-17
  • Interleukins
  • Receptors, Aryl Hydrocarbon
  • Receptors, Interleukin-21
  • Transforming Growth Factor beta
  • interleukin-21