Cytokine regulation of lung Th17 response to airway immunization using LPS adjuvant.
Cytokine regulation of lung Th17 response to airway immunization using LPS adjuvant.
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作者：
由气道细菌引起的感染优先诱导Th17反应。然而，参与肺中CD4 T细胞反应调节的机制尚不完全清楚。在这里，我们研究了以LPS作为佐剂免疫应答的肺中Th17分化调节的机制。我们的数据显示Myd88和TRIF都是Th17诱导所必需的。这种独特的命运决定可以通过气道给药LPS诱导的炎症细胞因子的模式来解释。我们发现小巨噬细胞产生IL-1β和IL-6，肺泡树突状细胞产生IL-23，有利于Th17反应，IL-10抑制IFN-γ的产生。此外，我们发现外源性IL-1β可以显著改变流感和淋巴细胞性脉络丛脑膜炎病毒感染模型驱动的Th1反应，并诱导IL-17的产生。因此，肺对潜在威胁的免疫反应的准确性是由细胞因子微环境精心策划的，可以通过改变细胞因子环境进行重极化和靶向治疗。这些结果表明，肺树突状细胞和巨噬细胞在响应LPS佐剂鼻内免疫时产生的细胞因子如何调节Th17反应的发展。
Infections caused by bacteria in the airway preferentially induce a Th17 response. However the mechanisms involved in the regulation of CD4 T cells responses in the lungs are incompletely understood. Here we have investigated the mechanisms involved in the regulation of Th17 differentiation in the lungs in response to immunization with LPS as adjuvant. Our data shows that both Myd88 and TRIF are necessary for Th17 induction. This distinctive fate determination can be accounted for by the pattern of inflammatory cytokines induced by airway administration of LPS. We identified the production of IL-1β and IL-6 by small macrophages and IL-23 by alveolar dendritic cells, favoring Th17 responses, and IL-10 repressing IFN-γ production. Furthermore, we show that exogenous IL-1β can drastically alter Th1 responses driven by influenza and lymphocytic choriomeningitis virus infection models and induce IL-17 production. Thus the precision of the lung immune responses to potential threats is orchestrated by the cytokine microenvironment, can be repolarized and targeted therapeutically by altering the cytokine milieu. These results indicate how the development of Th17 responses in the lung are regulated by the cytokines produced by lung dendritic cells and macrophages in response to intranasal immunization with LPS adjuvant.
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影响因子：
4.4
作者：
Desch, A. Nicole;Henson, Peter M.;Jakubzick, Claudia V.
通讯作者：
Jakubzick, Claudia V.
影响因子：
6
作者：
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DOI：
10.1073/pnas.0902745106
发表时间：
2009-04-28
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
8
作者：
通讯作者：
--
DOI：
10.1073/pnas.1513532112
发表时间：
2015-10-13
影响因子：
11.1
作者：
Linehan, Jonathan L.;Dileepan, Thamotharampillai;Jenkins, Marc K.
通讯作者：
Jenkins, Marc K.