| First Author | Kim JH | Year | 2005 |
| Journal | Am J Pathol | Volume | 167 |
| Issue | 5 | Pages | 1231-41 |
| PubMed ID | 16251408 | Mgi Jnum | J:102402 |
| Mgi Id | MGI:3607463 | Doi | 10.1016/s0002-9440(10)61211-4 |
| Citation | Kim JH, et al. (2005) Natural Killer T (NKT) Cells Attenuate Bleomycin-Induced Pulmonary Fibrosis by Producing Interferon-{gamma}. Am J Pathol 167(5):1231-41 |
| abstractText | 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. |
