淋巴 IKKα 的缺失会扰乱肺部免疫平衡、驱动 BALT 的形成并保护肺部免受流感侵袭

Q3 Medicine
Michelle D Cully, Julianne E Nolte, Athena Patel, Andrew E Vaughan, Michael J May
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引用次数: 0

摘要

IκB 激酶(IKK)α 控制着淋巴器官发育所需的非典型 NF-κB 信号传导。我们以前曾发现,在淋巴内皮细胞(LECs)中组成性缺乏IKKα的IkkαLyve-1小鼠中,淋巴结的形成被消减。我们现在发现,淋巴管内皮细胞中 IKKα 的缺失会导致肺部 BALT 的形成。三级淋巴结构只出现在IkkαLyve-1小鼠的肺部,而不出现在任何其他组织中,而且这些高度组织化的BALT结构是在出生后没有炎症的情况下形成的。此外,我们还发现,与同窝对照组相比,受到甲型流感病毒(IAV)挑战的 IkkαLyve-1 小鼠存活率明显提高,体重减轻。重要的是,我们确定 IkkαLyve-1 小鼠发病率和死亡率的改善与病毒载量和清除率无关,因为这两种小鼠控制和清除 IAV 感染的能力相似。相反,我们发现 IFN-γ 水平下降,CD8 T 细胞和单核细胞对 IkkαLyve-1 肺部的浸润减少。我们的结论是,消减 LECs 中的 IKKα 能促进 BALT 的形成,并通过减少促炎刺激降低 IkkαLyve-1 小鼠对 IAV 感染的易感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Loss of Lymphatic IKKα Disrupts Lung Immune Homeostasis, Drives BALT Formation, and Protects against Influenza.

IκB kinase (IKK)α controls noncanonical NF-κB signaling required for lymphoid organ development. We showed previously that lymph node formation is ablated in IkkαLyve-1 mice constitutively lacking IKKα in lymphatic endothelial cells (LECs). We now reveal that loss of IKKα in LECs leads to the formation of BALT in the lung. Tertiary lymphoid structures appear only in the lungs of IkkαLyve-1 mice and are not present in any other tissues, and these highly organized BALT structures form after birth and in the absence of inflammation. Additionally, we show that IkkαLyve-1 mice challenged with influenza A virus (IAV) exhibit markedly improved survival and reduced weight loss compared with littermate controls. Importantly, we determine that the improved morbidity and mortality of IkkαLyve-1 mice is independent of viral load and rate of clearance because both mice control and clear IAV infection similarly. Instead, we show that IFN-γ levels are decreased, and infiltration of CD8 T cells and monocytes into IkkαLyve-1 lungs is reduced. We conclude that ablating IKKα in LECs promotes BALT formation and reduces the susceptibility of IkkαLyve-1 mice to IAV infection through a decrease in proinflammatory stimuli.

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来源期刊
CiteScore
3.70
自引率
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