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Original Article
 

Immature Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase Suppress Ovalbumin-Induced Allergic Airway Inflammation in Mice
 

XJ An,1* CX Bai,2* JB Xia,3 T Dang,4 P Qian,5 GS Qian,1 W Liao6
*Both authors contributed equally to the manuscript.

1Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China
2Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai, People’s Republic of China
3Department of Pulmonary Medicine, First People’s Hospital of Hangzhou, Zhejiang Province, People’s Republic of China
4Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China
5Department of Ultrasound Diagnosis, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China
6Department of Pediatrics, Xinqiao Hospital, the Third Military Medical University, Chongqing, People’s Republic of China

J Investig Allergol Clin Immunol 2011; Vol. 21(3): 185-192
 

 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, MHC II, 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 IDOexpressing imDCs. Co-culture with IDO-expressing imDCs also induced apoptosis, inhibited IL-4 and IL-5 expression, and upregulated IFN-γ expression in CD4+ T cells.

Conclusions: IDO-expressing imDCs induced TH2 cell apoptosis and reduced TH2 cell activation and allergic airway inflammation in OVAsensitized mice. Thus, upregulation of IDO expression may provide a novel immunointervention strategy for asthma treatment.

Key words: Immune tolerance. Indoleamine 2,3-dioxygenase. Immature dendritic cell.