X J An1, C X Bai, J B Xia, T Dang, P Qian, G S Qian, W Liao. 1. Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
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.
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: Giuseppe Spaziano; Donato Cappetta; Konrad Urbanek; Elena Piegari; Grazia Esposito; Maria Matteis; Manuela Sgambato; Gioia Tartaglione; Rosa Russo; Raffaele De Palma; Francesco Rossi; Antonella De Angelis; Bruno D'Agostino Journal: Mediators Inflamm Date: 2016-12-20 Impact factor: 4.711