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.

译文

超敏性肺炎(HP)是由Th1免疫反应介导的。 NKT细胞通过调节Th1 / Th2平衡来调节免疫反应。因此,我们推测NKT细胞通过调节Th1 / Th2反应在HP的发展中起关键作用。为了解决此问题,我们探讨了NKT细胞在糖多孢菌直肠病毒(SR)诱导的HP中的功能作用。在CD1d(-/-)小鼠中,在组织学变化,羟脯氨酸水平,支气管肺泡灌洗液中CD4:CD8比值和SR特异性免疫反应方面,HP较对照组小鼠差。 CD1d(-/-)小鼠在HP期间在肺中显示升高的IFN-γ产生,这主要是由Gr-1中性粒细胞产生的。 CD1d(-/-)小鼠中IFN-γ的阻滞减弱了HP,而rIFN-γ的注射加重了HP。此外,在HP期间,Gr-1中性粒细胞的消耗减少了支气管肺泡灌洗液中CD8 T细胞的数量。 IL-4(-/-)小鼠NKT细胞的过继转移不会减弱HP,而野生型或IFN-γ(-/-)小鼠NKT细胞则抑制HP。总之,产生IL-4的NKT细胞通过抑制产生IFN-γ的嗜中性粒细胞在SR诱导的HP中起保护作用,该嗜中性粒细胞诱导肺中CD8 T细胞的活化和增殖。

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