Journal
INTERNATIONAL IMMUNOLOGY
Volume 22, Issue 6, Pages 503-513Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxq034
Keywords
airway inflammation; IFN-gamma; IL-17; neutrophilia; severe asthma
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
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Adoptive cell transfer of an ovalbumin (OVA)-specific T(h)17-polarized cell population from transgenic DO11.10 mice into BALB/c mice followed by OVA inhalation caused airway hyperresponsiveness (AHR) with severe neutrophilia. The transferred T(h)17 cell population previously polarized in vitro with IL-6, transforming growth factor-beta and IL-23-contained negligible numbers of IFN-gamma-producing cells; however, during T(h)17-cell-dependent airway inflammation, significant numbers of IFN-gamma-producing cells-including cells producing both IL-17 and IFN-gamma and cells producing only IFN-gamma-were detected in the lung in addition to cells producing only IL-17. Using T(h)17-polarized cell populations derived from IL-17(-/-) or IFN-gamma(-/-) mice, it was demonstrated that IL-17 is essential for inducing neutrophilic airway inflammation and that IFN-gamma is required for the AHR elevation. IFN-gamma appeared to be derived from cells producing both IL-17 and IFN-gamma and/or from cells producing only IFN-gamma, which were converted from the transferred T(h)17-polarized cell population. We also found that mAbs that neutralize IL-12 significantly suppressed the conversion of the T(h)17-polarized cell population toward IFN-gamma producers in the lung; concomitantly, with this decreased conversion, IL-12 neutralization also attenuated the AHR elevation in the lung. IL-12-dependent conversion of the transferred T(h)17-polarized cell population into IFN-gamma producers in the lung thus appeared to be a crucial process for inducing AHR elevation in T(h)17-cell-dependent airway inflammation.
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