Th2‐driven Innate Immune Responses in Carbon Nanotube‐induced Lung Fibrosis

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Aberrant tissue responses to persistent deposition of foreign bodies frequently result in organ fibrosis through orchestrated, but poorly understood processes. Carbon nanotubes are new nano materials that have found a broad range of applications in industrial and commercial products. Animal studies indicate that certaincarbon nanotubes behave as insoluble fibers that deposit in the lungs upon inhalation and stimulate a rapid onset pulmonary fibrotic response, characterized by inflammation, interstitial fibrosis, and granuloma formation. We have used multi‐walled carbon nanotubes (MWCNTs)‐induced mouse lung fibrosisas a model to analyze the molecular underpinnings of lung fibrosis induced by foreign bodies. Genome‐wide microarray analyses of the lungs exposed to MWCNTs revealed a range of differentially expressed genes involved in pathways of immune and inflammatory regulation, response to stress and extracellular stimuli, and cell migration and adhesion. In particular, the T helper 2(Th2)‐driven innate immune responses were significantly enriched. MWCNTs significantly induced the expression of Th2 cytokines, typified by interleukin(IL)‐4 and IL‐13, and a panel of Th2 signature downstream genes, such as Il4i1, Chia, and Ccl11/Eotaxin. Induction involved the activation of STAT6 via the phosphorylation of STAT6 and the up‐regulation of GATA‐3 that directly controls the transcription of Th2 target genes. These findings demonstrate the activation of Th2‐driven innate immune responses during the development of lung fibrosis induced by carbon nanotubes, providing a molecular link between Th2functions and the tissue response to foreign body deposition in mammalian lungs.Support or Funding InformationSupported by a fund to QM from National Institute for Occupational Safety and Health, Health Effects Laboratory Division and Nanotechnology Research Center.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.