IL-4-secreting NKT cells prevent hypersensitivity pneumonitis by suppressing IFN-gamma-producing neutrophils.
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-gamma production in the lung during the HP, and this was produced mainly by Gr-1+ neutrophils. The blockade of IFN-gamma in CD1d(-/-) mice attenuated the HP, whereas the injection of rIFN-gamma 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-gamma(-/-) mouse NKT cells suppressed the HP. In conclusion, NKT cells producing IL-4 play a protective role in SR-induced HP by suppressing IFN-gamma-producing neutrophils, which induce the activation and proliferation of CD8+ T cells in the lung.
Hwang
Su Jin
SJ
Department of Pathology, Graduate Program of Immunology, Seoul National University College of Medicine, Seoul, Korea.
Kim
Sanghee
S
Park
Weon Seo
WS
Chung
Doo Hyun
DH
D000542:Alveolitis, Extrinsic Allergic / Q000209:etiology* / Q000276:immunology / Q000382:microbiology; D000818:Animals; D018949:Antigens, CD1; D055610:Antigens, CD1d; D018414:CD8-Positive T-Lymphocytes; D002450:Cell Communication; D049109:Cell Proliferation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D015847:Interleukin-4 / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D016930:Saccharopolyspora; D013601:T-Lymphocytes
D018949:Antigens, CD1; D055610:Antigens, CD1d; D015847:Interleukin-4; D007371:Interferon-gamma