Browsing by Subject "MDSCs"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Innate Immune Pathways Associated with Lung Radioprotection by Soy Isoflavones
    (Frontiers, 2017-01-23) Abernathy, Lisa M.; Fountain, Matthew D.; Joiner, Michael C.; Hillman, Gilda G.; Department of Microbiology & Immunology, IU School of Medicine
    INTRODUCTION: Radiation therapy for lung cancer causes pneumonitis and fibrosis. Soy isoflavones protect against radiation-induced lung injury, but the mediators of radioprotection remain unclear. We investigated the effect of radiation on myeloid-derived suppressor cells (MDSCs) in the lung and their modulation by soy isoflavones for a potential role in protection from radiation-induced lung injury. METHODS: BALB/c mice (5-6 weeks old) received a single 10 Gy dose of thoracic irradiation and soy isoflavones were orally administrated daily before and after radiation at 1 mg/day. Arginase-1 (Arg-1) and nuclear factor κB (NF-κB) p65 were detected in lung tissue by western blot analysis and immunohistochemistry. Lung MDSC subsets and their Arg-1 expression were analyzed by flow cytometry. Cytokine levels in the lungs were measured by ELISA. RESULTS: At 1 week after radiation, CD11b+ cells expressing Arg-1 were decreased by radiation in lung tissue yet maintained in the lungs treated with radiation and soy isoflavones. Arg-1 was predominantly expressed by CD11b+Ly6ClowLy6G+ granulocytic MDSCs (gr-MDSCs). Arg-1 expression in gr-MDSCs was reduced by radiation and preserved by supplementation with soy isoflavones. A persistent increase in Arg-1+ cells was observed in lung tissue treated with combined radiation and soy isoflavones at early and late time points, compared to radiation alone. The increase in Arg-1 expression mediated by soy isoflavones could be associated with the inhibition of radiation-induced activation of NF-κB and the control of pro-inflammatory cytokine production demonstrated in this study. CONCLUSION: A radioprotective mechanism of soy isoflavones may involve the promotion of Arg-1-expressing gr-MDSCs that could play a role in downregulation of inflammation and lung radioprotection.
  • Thumbnail Image
    Item
    Metabolic reprogramming of myeloid-derived suppressive cells
    (Impact Journals, 2017-04-28) Du, Hong; Ding, Xinchun; Yan, Cong; Pathology and Laboratory Medicine, School of Medicine
  • Thumbnail Image
    Item
    Myeloid-Derived Suppressor Cells Impair Alveolar Macrophages through PD-1 Receptor Ligation during Pneumocystis Pneumonia
    (American Society for Microbiology, 2015-02) Lei, Guang-Sheng; Zhang, Chen; Lee, Chao-Hung; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Myeloid-derived suppressor cells (MDSCs) were recently found to accumulate in the lungs during Pneumocystis pneumonia (PcP). Adoptive transfer of these cells caused lung damage in recipient mice, suggesting that MDSC accumulation is a mechanism of pathogenesis in PcP. In this study, the phagocytic activity of alveolar macrophages (AMs) was found to decrease by 40% when they were incubated with MDSCs from Pneumocystis-infected mice compared to those incubated with Gr-1+ cells from the bone marrow of uninfected mice. The expression of the PU.1 gene in AMs incubated with MDSCs also was decreased. This PU.1 downregulation was due mainly to decreased histone 3 acetylation and increased DNA methylation caused by MDSCs. MDSCs were found to express high levels of PD-L1, and alveolar macrophages (AMs) were found to express high levels of PD-1 during PcP. Furthermore, PD-1 expression in AMs from uninfected mice was increased by 18-fold when they were incubated with MDSCs compared to those incubated with Gr-1+ cells from the bone marrow of uninfected mice. The adverse effects of MDSCs on AMs were diminished when the MDSCs were pretreated with anti-PD-L1 antibody, suggesting that MDSCs disable AMs through PD-1/PD-L1 ligation during PcP.