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Type I Interferon signaling controls the accumulation and transcriptomes of monocytes in the aged lung

机译:I型干扰素信号传导控制老年肺中单核细胞的累积和转录组

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Aging is paradoxically associated with a deteriorated immune defense (immunosenescence) and increased basal levels of tissue inflammation (inflammaging). The lung is particularly sensitive to the effects of aging. The immune cell mechanisms underlying physiological lung aging remain poorly understood. Here we reveal that aging leads to increased interferon signaling and elevated concentrations of chemokines in the lung, which is associated with infiltration of monocytes into the lung parenchyma. scRNA-seq identified a novel Type-1 interferon signaling dependent monocyte subset (MO-ifn) that upregulated IFNAR1 expression and exhibited greater transcriptomal changes with aging than the other monocytes. Blockade of type-1 interferon signaling by treatment with anti-IFNAR1 neutralizing antibodies rapidly ablated MO-ifn cells. Treatment with anti-IFNAR1 antibodies also reduced airway chemokine concentrations and repressed the accumulation of the overall monocyte population in the parenchyma of the aged lung. Together, our work suggests that physiological aging is associated with increased basal level of airway monocyte infiltration and inflammation in part due to elevated type-1 interferon signaling.
机译:衰老与劣化的免疫防御(免疫倒期)和增加的组织炎症(炎性)矛盾的矛盾有关。肺对老化的影响特别敏感。生理肺衰老的免疫细胞机制仍然明显差不多。在这里,我们揭示老化导致肺中的干扰素信号传导和升高的趋化因子浓度增加,这与单核细胞浸润到肺实质中的渗透相关。 ScRNA-SEQ鉴定了一种新型1型干扰素信号依赖性单核细胞子集(MO-IFN),其上调IFNAR1表达,并且表现出比其他单核细胞的老化更大的转录常数变化。通过用抗IFNAR1中和抗体迅速烧蚀MO-IFN细胞的抗IFNAR1中和抗体阻断1型干扰素信号传导。用抗IFNAR1抗体治疗还减少了气道趋化因子浓度,并在龄肺部的实质中压制了整个单核细胞群的积累。我们的作品在一起表明,由于1型干扰素信号传导,生理老化与呼吸道单核细胞浸润和炎症的增加的基础水平。

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