title: Immature dendritic cells expressing indoleamine 2,3-dioxygenase suppress ovalbumin-induced allergic airway inflammation in mice.
abstract: BACKGROUND
  Proliferation of activated CD4+ T lymphocytes is inhibited by indoleamine 2,3-dioxygenase (IDO).
  
  
  OBJECTIVE
  We undertook the present study to test the hypothesis that IDO-expressing immature DCs (imDCs) can restore immune tolerance in mice suffering from allergic airway inflammation.
  
  
  METHODS
  imDCs were generated from murine bone marrow cells using granulocyte-macrophage colony-stimulating factor.The imDCs were subsequently transfected with an IDO expression vector (pEGFP-N1-IDO). Surface marker expression, including CD11c, MHCII, CD80, and CD86, was analyzed using flow cytometry. IDO-expressing imDCs were injected into the trachea of ovalbumin (OVA)-sensitized mice, and lung histopathology and cytokine expression in bronchoalveolar lavage fluid were assessed. The splenic CD4+ T cells of OVA-sensitized mice were isolated and co-cultured with pEGFP-N1-IDO-expressing imDCs, and apoptosis of CD4+ T cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay.
  
  
  RESULTS
  Expression of IDO in imDCs did not alter cell surface molecule expression. We observed marked lung inflammation, elevated total cell and eosinophil count, and altered cytokine levels in OVA-sensitized mice. These parameters improved upon inoculation with IDO-expressing imDCs. Co-culture with IDO-expressing imDCs also induced apoptosis, inhibited IL-4 and IL-5 expression, and upregulated IFN-gamma expression in CD4+ T cells.
  
  
  CONCLUSIONS
  IDO-expressing imDCs induced T(H)2 cell apoptosis and reduced T(H)2 cell activation and allergic airway inflammation in OVA-sensitized mice. Thus, upregulation of IDO expression may provide a novel immunointervention strategy for asthma treatment.
authors.affiliation: Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: X J
authors.initials: XJ
authors.lastname: An
authors.forename: C X
authors.initials: CX
authors.lastname: Bai
authors.forename: J B
authors.initials: JB
authors.lastname: Xia
authors.forename: T
authors.initials: T
authors.lastname: Dang
authors.forename: P
authors.initials: P
authors.lastname: Qian
authors.forename: G S
authors.initials: GS
authors.lastname: Qian
authors.forename: W
authors.initials: W
authors.lastname: Liao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005802:Genes, MHC Class II; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology* / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin