title: In vivo induction of Tr1 cells via mucosal dendritic cells and AHR signaling.
abstract: 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.
  
  
  RESULTS
  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
  Our findings identify a unique approach to generate Tr1 cells in vivo and provide insights into the mechanisms by which these cells are induced.
authors: Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Henry Yim
authors: HY
authors: Wu
authors: Francisco J
authors: FJ
authors: Quintana
authors: Andre Pires
authors: AP
authors: da Cunha
authors: Benjamin T
authors: BT
authors: Dake
authors: Thomas
authors: T
authors: Koeglsperger
authors: Sarah C
authors: SC
authors: Starossom
authors: Howard L
authors: HL
authors: Weiner
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D015551:Autoimmunity / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D053655:Receptors, Interleukin-21 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D000906:Antibodies; D017252:CD3 Complex; D020381:Interleukin-17; D007378:Interleukins; D018336:Receptors, Aryl Hydrocarbon; D053655:Receptors, Interleukin-21; D016212:Transforming Growth Factor beta; D000098546:Interleukin-21