Type I Interferon Signaling Increases Versican Expression and Synthesis in Lung Stromal Cells During Influenza Infection
Type I Interferon Signaling Increases Versican Expression and Synthesis in Lung Stromal Cells During Influenza Infection
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DOI：
10.1369/00221554211054447
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发表时间：
2021-10-19
影响因子：
3.2
通讯作者：
Frevert, Charles W.
中科院分区：
文献类型：
--
作者：
Brune, Jourdan E.;Chang, Mary Y.;Frevert, Charles W.
Versican是一种硫酸软骨素蛋白聚糖，是炎症性肺病中细胞外基质（ECM）的重要成分。Versican作为免疫调节分子的潜力使其成为控制肺部宿主免疫反应的有希望的治疗靶点。为了确定甲型流感病毒性肺炎过程中多功能蛋白聚糖表达和积累的变化，我们记录了多功能蛋白聚糖mRNA和蛋白质与肺部炎症细胞浸润的时间和空间变化。这些研究在用甲型流感病毒感染后第3、6、9和12天在野生型C57 BL 6/J小鼠的肺中使用免疫组织化学、原位杂交和定量数字病理学进行。使用双链体原位杂交，我们证明，I型干扰素信号显着有助于多功能蛋白聚糖在肺间质细胞的表达。我们的研究结果表明，多功能蛋白聚糖是一种I型干扰素刺激的基因在肺成纤维细胞和周细胞的情况下，病毒性肺炎。这些数据也为未来的研究提供了指导，以确定多功能蛋白聚糖在流感感染的肺部免疫应答中的作用：
Versican, a chondroitin sulfate proteoglycan, is an essential component of the extracellular matrix (ECM) in inflammatory lung disease. Versican's potential as an immunomodulatory molecule makes it a promising therapeutic target for controlling host immune responses in the lungs. To establish changes to versican expression and accumulation during influenza A viral pneumonia, we document the temporal and spatial changes to versican mRNA and protein in concert with pulmonary inflammatory cell infiltration. These studies were performed in the lungs of wild-type C57BL6/J mice on days 3, 6, 9, and 12 post-infection with influenza A virus using immunohistochemistry, in situ hybridization, and quantitative digital pathology. Using duplex in situ hybridization, we demonstrate that type I interferon signaling contributes significantly to versican expression in lung stromal cells. Our findings show that versican is a type I interferon-stimulated gene in pulmonary fibroblasts and pericytes in the context of viral pneumonia. These data also provide a guide for future studies to determine the role of versican in the pulmonary immune response to influenza infection: