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-Producing Neutrophils1
* Department of Pathology and
Laboratory of Immune Regulation, Graduate Program of Immunology, Seoul National University College of Medicine, Seoul, Korea;
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea; and
Division of Specific Organ Cancers, National Cancer Center, Goyang, Gyeonggi, Korea
Hypersensitivity pneumonitis (HP) is mediated by Th1 immune response. NKT cells regulate immune responses by modulating the Th1/Th2 balance. Therefore, we postulated that NKT cells play a critical role in the development of the HP by modulating the Th1/Th2 response. To address this issue, we explored the functional roles of NKT cells in Saccharopolyspora rectivirgula (SR)-induced HP. In CD1d–/– mice, the HP was worse in terms of histological changes, hydroxyproline levels, the CD4:CD8 ratio in bronchoalveolar lavage fluid, and SR-specific immune responses than in control mice. CD1d–/– mice showed elevated IFN-
production in the lung during the HP, and this was produced mainly by Gr-1+ neutrophils. The blockade of IFN- in CD1d–/– mice attenuated the HP, whereas the injection of rIFN- aggravated it. Moreover, the depletion of Gr-1+ neutrophils reduced CD8+ T cell numbers in bronchoalveolar lavage fluid during the HP. The adoptive transfer of IL-4–/– mouse NKT cells did not attenuate the HP, whereas wild-type or IFN-–/– mouse NKT cells suppressed the HP. In conclusion, NKT cells producing IL-4 play a protective role in SR-induced HP by suppressing IFN--producing neutrophils, which induce the activation and proliferation of CD8+ T cells in the lung.
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1 This work was supported by Grant 03-2006-014 from the Seoul National University Hospital Research Fund and the National Research Laboratory Program (Grant 2005-01319), and National R & D Program. Ministry of Science and Technology, Republic of Korea.
2 Address correspondence and reprint requests to Dr. Doo Hyun Chung, Department of Pathology and Laboratory of Immune Regulation, Graduate Program of Immunology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea. E-mail address: doohyun{at}plaza.snu.ac.kr
3 Abbreviations used in this paper: HP, hypersensitivity pneumonitis; BALF, bronchoalveolar lavage fluid; SR, Saccharopolyspora rectivirgula; WT, wild type.
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