中性粒细胞
免疫学
生物
趋化因子
渗透(HVAC)
炎症
CXCL1型
过继性细胞移植
肺
发病机制
免疫系统
医学
T细胞
内科学
热力学
物理
作者
Sandra Hoegl,Heidi Ehrentraut,Kelley S. Brodsky,Francisco Victorino,Lucy Golden-Mason,Holger K. Eltzschig,Eóin N. McNamee
标识
DOI:10.1189/jlb.3a0516-227r
摘要
Abstract A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment of polymorphonuclear neutrophils (PMNs) into the lungs, causing significant collateral tissue damage. Defining the molecular and cellular steps that control neutrophil infiltration and activation during ALI is therefore of important therapeutic relevance. Based on previous findings implicating the transcription factor Tbet in mucosal Th1-inflammation, we hypothesized a detrimental role for Tbet during ALI. In line with our hypothesis, initial studies of endotoxin-induced lung injury revealed a marked protection of Tbet−/− mice, including attenuated neutrophilia compared to WT counterparts. Surprisingly, subsequent studies identified natural killer (NK) cells as the major source of pulmonary Tbet during ALI. In addition, a chemokine screen suggested that mature Tbet+ NK-cells are critical for the production of pulmonary CXCL1 and -2, thereby contributing to pulmonary PMN recruitment. Indeed, both NK-cell Ab depletion and adoptive transfer studies provide evidence for NK cells in the orchestration of neutrophil recruitment during endotoxin-induced ALI. Taken together, these findings identify a novel role for Tbet+ NK-cells in initiating the early events of noninfectious pulmonary inflammation.
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