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- W2964277546 abstract "e21097 Background: Radiation pneumonitis is a substantial cause of morbidity and mortality with thoracic radiation for lung cancer. Little is known about the crucial mechanisms of the inflammatory response. We seek to determine if a key mediator of organ-specific inflammatory disorders and innate immune response, IL-17 + γδ T cells, is associated with radiation pneumonitis. Methods: C3HBe/FeJ mice (7 mice/group) were sham-irradiated as controls or exposed to a single dose of 15 Gy thoracic X-ray to develop pneumonitis. We have previously shown that TGFβ has an immunosuppressive activity in radiation pneumonitis. To potentiate the radiation pneumonitis, one group of mice was administered anti-TGFβ therapy with inhibitory TGFβ mAb (1D11, i.p.10 mg/kg/wk). Bronchoalveolar lavage fluid was assessed for cytology and inflammatory cytokine level. Lung tissues were examined for cell infiltration and histopathological changes. Cell surface marker and intracellular cytokine staining were performed on lymphocytes from the digested lungs by flow cytometry. Results: At 10 weeks post-irradiation, the lungs of the irradiated mice showed substantially more alveolar wall edema and increased infiltration of inflammatory cells compared with sham controls. Pneumonitis-involved lungs contained more IL-17 + γδ T cells (0.85% ± 0.00%) compared with sham controls (0.33% ± 0.02%), p<0.001. Furthermore increased IL-17 + γδ T cells were associated with potentiated radiation pneumonitis with anti-TGFβ therapy. There was a significant increased alveolar inflammation in irradiated mice injected with anti-TGFβ mAb. Anti-TGFβ irradiated lungs also contained significantly more IL-17 + γδ T cells (1.17% ± 0.13%) compared with irradiated controls (0.72% ± 0.13%), p<0.001. There was no increase of other TGFβ-dependent T cell subtypes such as IFNγ + αβ T cells (Th1), IL-17 + αβ T cells (Th17), CD25 + Foxp3 + Tregs, nor activated macrophages in the potentiated pneumonitis lungs. Conclusions: Our findings implicate a novel role for IL17-expressing γδ T cells in radiation pneumonitis. This study reveals this innate immune response pathway as a potential target for therapeutic intervention in radiation lung injury" @default.
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- W2964277546 date "2012-05-20" @default.
- W2964277546 modified "2023-10-01" @default.
- W2964277546 title "Association of IL17-expressing γδ t cells with acute radiation-induced pneumonitis." @default.
- W2964277546 doi "https://doi.org/10.1200/jco.2012.30.15_suppl.e21097" @default.
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