Browsing by Author "Song, Lizhen"

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    Chronic exposure to carbon black ultrafine particles reprograms macrophage metabolism and accelerates lung cancer
    (AAAS, 2022) Chang, Cheng-Yen; You, Ran; Armstrong, Dominique; Bandi, Ashwini; Cheng, Yi-Ting; Burkhardt, Philip M.; Becerra-Dominguez, Luis; Madison, Matthew C.; Tung, Hui-Ying; Zeng, Zhimin; Wu, Yifan; Song, Lizhen; Phillips, Patricia E.; Porter, Paul; Knight, John M.; Putluri, Nagireddy; Yuan, Xiaoyi; Marcano, Daniela C.; McHugh, Emily A.; Tour, James M.; Catic, Andre; Maneix, Laure; Burt, Bryan M.; Lee, Hyun-Sung; Corry, David B.; Kheradmand, Farrah
    Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A–dependent emphysema. However, whether and how they alter the immune responses to lung cancer remains unknown. Here, we show that exposure to nCB particles increased PD-L1+ PD-L2+ CD206+ antigen-presenting cells (APCs), exhausted T cells, and Treg cells. Lung macrophages that harbored nCB particles showed selective mitochondrial structure damage and decreased oxidative respiration. Lung macrophages sustained the HIF1α axis that increased glycolysis and lactate production, culminating in an immunosuppressive microenvironment in multiple mouse models of non–small cell lung cancers. Adoptive transfer of lung APCs from nCB-exposed wild type to susceptible mice increased tumor incidence and caused early metastasis. Our findings show that nCB exposure metabolically rewires lung macrophages to promote immunosuppression and accelerates the development of lung cancer.
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    Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema
    (eLife Sciences Publications Ltd., 2015) You, Ran; Lu, Wen; Shan, Ming; Berlin, Jacob M.; Samuel, Errol L.G.; Marcano, Daniela C.; Sun, Zhengzong; Sikkema, William K.A.; Yuan, Xiaoyi; Song, Lizhen; Hendrix, Amanda Y.; Tour, James M.; Corry, David B.; Kheradmand, Farrah
    Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.