Critical role of IL-17RA in immunopathology of influenza infection.
Critical role of IL-17RA in immunopathology of influenza infection.
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DOI：
10.4049/jimmunol.0900995
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发表时间：
2009-10-15
期刊：
影响因子：
--
通讯作者：
Kolls JK
中科院分区：
文献类型：
--
作者：
Crowe CR;Chen K;Pociask DA;Alcorn JF;Krivich C;Enelow RI;Ross TM;Witztum JL;Kolls JK
流感感染引起的急性肺损伤与高死亡率、空气中中性粒细胞增加以及组织髓过氧化物酶(MPO)增加有关。由于IL-17受体拮抗剂(IL-17RA)的配体IL-17A和IL-17F在内毒素或革兰氏阴性细菌性肺炎中介导中性粒细胞向肺内迁移，我们推测IL-17RA信号在肺流感感染所致的急性肺损伤中起关键作用。IL-17RA在流感感染后体重减轻、中性粒细胞迁移和组织髓过氧化物酶(MPO)升高方面起关键作用。然而，IL-17RA对流感血凝素或核衣壳蛋白特异的CD8+T细胞的募集是必不可少的。与此一致，IL-17RA不是病毒清除所必需的。然而，在流感感染的背景下，IL-17RA−/−小鼠的氧化磷脂水平显著降低，此前已证明，氧化磷脂是包括流感感染和胃酸吸入在内的几种急性肺损伤模型的重要介质。综上所述，这些数据支持靶向IL-17或IL-17RA治疗急性病毒感染所致的急性肺损伤。
Acute lung injury due to influenza infection is associated with high mortality, an increase in neutrophils in the airspace, and increases in tissue myeloperoxidase (MPO). Because IL-17A and IL-17F, ligands for IL-17 receptor antagonist (IL-17RA), have been shown to mediate neutrophil migration into the lung in response to LPS or Gram-negative bacterial pneumonia, we hypothesized that IL-17RA signaling was critical for acute lung injury in response to pulmonary influenza infection. IL-17RA was critical for weight loss and both neutrophil migration and increases in tissue myeloperoxidase (MPO) after influenza infection. However, IL-17RA was dispensable for the recruitment of CD8+ T cells specific for influenza hemagglutinin or nucleocapsid protein. Consistent with this, IL-17RA was not required for viral clearance. However, in the setting of influenza infection, IL-17RA−/− mice showed significantly reduced levels of oxidized phospholipids, which have previously been shown to be an important mediator in several models of acute lung injury, including influenza infection and gastric acid aspiration. Taken together, these data support targeting IL-17 or IL-17RA in acute lung injury due to acute viral infection.
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影响因子：
6.5
作者：
Hartvigsen, Karsten;Chou, Meng-Yun;Witztum, Joseph L.
通讯作者：
Witztum, Joseph L.
DOI：
10.4049/jimmunol.0801814
发表时间：
2009-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hamada H;Garcia-Hernandez Mde L;Reome JB;Misra SK;Strutt TM;McKinstry KK;Cooper AM;Swain SL;Dutton RW
通讯作者：
Dutton RW
影响因子：
8.8
作者：
Abraham, E
通讯作者：
Abraham, E
影响因子：
4.8
作者：
Aggarwal, S;Ghilardi, N;Gurney, AL
通讯作者：
Gurney, AL
影响因子：
5.4
作者：
Bot, A;Bot, S;Bona, CA
通讯作者：
Bona, CA