Natural killer T (NKT) cells attenuate bleomycin-induced pulmonary fibrosis by producing interferon-gamma

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Kim, Ji Hyung; Kim, Hye Young; Kim, Sanghee; Chung, Jin-Haeng; Park, Weon Seo; Chung, Doo Hyun
Issue Date
American Society for Investigative Pathology
Am J Pathol 2005, 167:1231-1241
Adoptive TransferAnimalsBleomycinBody WeightCells, CulturedDisease Models, AnimalHydroxyproline/analysisInterferon-gamma/*biosynthesis/geneticsKiller Cells, Natural/*immunologyLung/drug effects/*pathologyMaleMiceMice, Inbred C57BLMice, KnockoutPulmonary Fibrosis/chemically induced/*immunology/*pathologyT-Lymphocyte Subsets/*immunologyTransforming Growth Factor beta/metabolismTransforming Growth Factor beta1
Pulmonary fibrosis is a progressive illness characterized by interstitial fibrosis. Although the precise mechanism for pulmonary fibrosis is not completely understood, an immune response involving interferon (IFN)-gamma appears to play a role. Therefore, we examined the functional roles of natural killer T (NKT) cells, which produce IFN-gamma and interleukin-4 on activation, in bleomycin-induced pulmonary fibrosis. In NKT cell-deficient mice, pulmonary fibrosis was worse in terms of histology, hydroxyproline levels, and mortality than in control mice. The transforming growth factor (TGF)-beta1 levels were higher in the lung after injecting bleomycin, and blockade of TGF-beta1 by neutralizing monoclonal antibody attenuated the pulmonary fibrosis in CD1d-/- mice. In contrast, the production of IFN-gamma was reduced in lungs from CD1d-/- mice. Moreover, the adoptive transfer of NKT cells into CD1d-/- mice increased IFN-gamma and reduced TGF-beta1 production, attenuating pulmonary fibrosis. An in vitro assay demonstrated that IFN-gamma was involved in suppressing TGF-beta1 production in cells collected from bronchoalveolar lavage. The adoptive transfer of NKT cells from IFN-gamma-/- mice did not reverse pulmonary fibrosis or TGF-beta1 production in lungs of CD1d-/- mice whereas NKT cells from B6 control mice attenuated fibrosis and reduced TGF-beta1 production. In conclusion, IFN-gamma-producing NKT cells play a novel anti-fibrotic role in pulmonary fibrosis by regulating TGF-beta1 production.
0002-9440 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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