T cell-directed IL-17 production by lung granular γδ T cells is coordinated by a novel IL-2 and IL-1β circuit.
T cell-directed IL-17 production by lung granular γδ T cells is coordinated by a novel IL-2 and IL-1β circuit.
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肺颗粒γδ T细胞的T细胞导向的IL-17产生由新的IL-2和IL-1β回路协调。
DOI：
10.1038/s41385-018-0037-0
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发表时间：
2018-09
影响因子：
8
通讯作者：
Vella AT
中科院分区：
文献类型：
--
作者：
Ménoret A;Buturla JA;Xu MM;Svedova J;Kumar S;Rathinam VAK;Vella AT
Immune-mediated lung is considered the result of an exacerbated innate injury immune response, although a role for adaptive lymphocytes is emerging. αβ T cells specific for S. aureus enterotoxin A orchestrate a Tγδ17 response during lung injury. However, the mechanism driving IL-17 production is unclear. Here, we show a role for IL-2 triggering IL-17 production by lung granular γδ T cells as IL-17 synthesis and neutrophil recruitment was reduced by IL-2 blocking mAbs in vitro and in vivo. Mass cytometry analysis revealed that lung γδ T cells responded directly to IL-2 as evident from STAT5 phosphorylation and RoRγt expression. IL-2 receptor blocking mAbs and JAK inhibition impaired STAT5 phosphorylation and IL-17 release. Moreover, inhalation of S. aureus enterotoxin A induced IL-2 secretion and caspase-1-dependent IL-1β activation to drive IL-17 production. This T-cell-mediated inflammasome-dependent IL-17 response is maximum when lung Tγδ17 cells were sequentially stimulated first with IL-2 then IL-1β. Interestingly, when IL-2 is given therapeutically to cancer patients it carries a known risk of lung injury that is largely indistinguishable from that seen in sepsis. Hence, this novel mechanism reveals therapeutic targets treating both acute lung injury and high-dose IL-2 toxicity in cancer.
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DOI：
10.1097/shk.0b013e31828f9c92
发表时间：
2013-05
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Bosmann M;Grailer JJ;Russkamp NF;Ruemmler R;Zetoune FS;Sarma JV;Ward PA
通讯作者：
Ward PA
影响因子：
64.5
作者：
Benci JL;Xu B;Qiu Y;Wu TJ;Dada H;Twyman-Saint Victor C;Cucolo L;Lee DSM;Pauken KE;Huang AC;Gangadhar TC;Amaravadi RK;Schuchter LM;Feldman MD;Ishwaran H;Vonderheide RH;Maity A;Wherry EJ;Minn AJ
通讯作者：
Minn AJ
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1097/shk.0000000000000188
发表时间：
2014-08
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Gores KM;Delsing AS;Kraus SJ;Powers L;Vaena DA;Milhem MM;Monick M;Doerschug KC
通讯作者：
Doerschug KC
DOI：
10.4049/jimmunol.1500054
发表时间：
2015-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
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
通讯作者：
Sheppard D