Unexpected Role for Adaptive αβTh17 Cells in Acute Respiratory Distress Syndrome.
Unexpected Role for Adaptive αβTh17 Cells in Acute Respiratory Distress Syndrome.
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DOI：
10.4049/jimmunol.1500054
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发表时间：
2015-07-01
期刊：
影响因子：
--
通讯作者：
Sheppard D
中科院分区：
文献类型：
--
作者：
Li JT;Melton AC;Su G;Hamm DE;LaFemina M;Howard J;Fang X;Bhat S;Huynh KM;O'Kane CM;Ingram RJ;Muir RR;McAuley DF;Matthay MA;Sheppard D
Acute respiratory distress syndrome (ARDS) is a devastating disorder characterized by increased alveolar permeability with no effective treatment beyond supportive care. Current mechanisms underlying ARDS focus on alveolar endothelial and epithelial injury caused by products of innate immune cells and platelets. However, the role of adaptive immune cells in ARDS remains largely unknown. Here we report that expansion of antigen-specific αβT helper 17 (αβTH17) cells contribute to ARDS by local secretion of IL-17A, which in turn directly increases alveolar epithelial permeability. Mice with a highly restrictive defect in antigen-specific αβTH17 cells were protected from experimental ARDS induced by a single dose of endotracheal lipopolysaccharide (LPS). Loss of IL-17 receptor C or antibody blockade of IL-17A was similarly protective, further suggesting that IL-17A released by these cells was responsible for this effect. LPS induced a rapid and specific clonal expansion of αβTH17 cells in the lung, as determined by deep sequencing of the hypervariable CD3RβVJ region of the T cell receptor. Our findings could be relevant to ARDS in humans, since we found significant elevation of IL-17A in bronchoalveolar lavage (BAL) fluid from patients with ARDS and recombinant IL-17A directly increased permeability across cultured human alveolar epithelial monolayers. These results reveal a previously unexpected role for adaptive immune responses that increase alveolar permeability in ARDS and suggest that αβTH17 cells and IL-17A could be novel therapeutic targets for this currently untreatable disease.
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