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

Ji Hyung Kim, Hye Young Kim, Sanghee Kim, Jin Haeng Chung, Weon Seo Park, Doo Hyun Chung

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Abstract

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)-γ appears to play a role. Therefore, we examined the functional roles of natural killer T (NKT) cells, which produce IFN-γ 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 to control mice. The transforming growth factor (TGF)-β1 levels were higher in the lung after injecting bleomycin, and blockade of TGF-β1 by neutralizing monoclonal antibody attenuated the pulmonary fibrosis in CD1d -/- mice. In contrast, the production of IFN-γ was reduced in lungs from CD1d -/- mice. Moreover, the adoptive transfer of NKT cells into CD1d -/- mice increased IFN-γ and reduced TGF-β1 production, attenuating pulmonary fibrosis. An in vitro assay demonstrated that IFN-γ was involved in suppressing TGF-β1 production in cells collected from bronchoalveolar lavage. The adoptive transfer of NKT cells from IFN-γ -/- mice did not reverse pulmonary fibrosis or TGF-β1 production in lungs of CD1d -/- mice whereas NKT cells from B6 control mice attenuated fibrosis and reduced TGF-β1 production. In conclusion, IFN-γ-producing NKT cells play a novel anti-fibrotic role in pulmonary fibrosis by regulating TGF-β1 production.

Original languageEnglish
Pages (from-to)1231-1241
Number of pages11
JournalAmerican Journal of Pathology
Volume167
Issue number5
DOIs
Publication statusPublished - 2005 Jan 1
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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