A Th17-polarized cell population that has infiltrated the lung requires cells that convert to IFN-γ production in order to induce airway hyperresponsiveness

被引:18
作者
Ashino, Shigeru [1 ]
Wakita, Daiko [2 ]
Shiohama, Yasuo [1 ]
Iwakura, Yoichiro [3 ]
Chamoto, Kenji [1 ]
Ohkuri, Takayuki [1 ]
Kitamura, Hidemitsu [1 ]
Nishimura, Takashi [1 ,2 ]
机构
[1] Hokkaido Univ, Inst Med Genet, Sect Dis Control, Div lmmunoregulat, Sapporo, Hokkaido 0010021, Japan
[2] Hokkaido Univ, Inst Med Genet, Div ROYCE Hlth Biosci, Sapporo, Hokkaido 0010021, Japan
[3] Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol, Tokyo 1088639, Japan
关键词
airway inflammation; IFN-gamma; IL-17; neutrophilia; severe asthma; SEVERE ASTHMA; HOST-DEFENSE; MOUSE MODEL; T-CELLS; TH17; IL-17; INFLAMMATION; SPUTUM; IL-23; INTERLEUKIN-17;
D O I
10.1093/intimm/dxq034
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:503 / 513
页数:11
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