Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia.
Pulmonary immune cell transcriptome changes in double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia.
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绒毛膜羊膜炎和产后高氧双重打击BPD模型中肺免疫细胞转录组的变化。
DOI：
10.1038/s41390-020-01319-z
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发表时间：
2021-09
影响因子：
3.6
通讯作者：
Alapati D
中科院分区：
文献类型：
--
作者：
Shrestha D;Ye GX;Stabley D;Betal SGN;Zhu Y;Glazewski L;Holbrook J;Sethi M;Hesek A;Shaffer TH;Aghai ZH;Addya S;Alapati D
患有支气管肺发育不良（BPD）的早产儿与环境病原体暴露相关的呼吸道疾病风险终身增加，其潜在机制尚不清楚。肺的常驻免疫细胞在宿主防御中起着至关重要的作用。然而，与BPD相关的围产期事件对肺特异性免疫细胞的影响尚不清楚。我们使用了产前绒毛膜炎和出生后高氧诱导的BPD的双重打击模型，并对所有常驻肺免疫细胞进行了全局转录组分析。我们发现趋化因子介导的信号传导和免疫细胞趋化性相关基因显著上调，多种T淋巴细胞功能相关基因下调。参与T细胞受体信号传导的多个基因下调，尽管在常氧下恢复6周，但在2月龄时Cd8a基因表达仍下调。此外，CD8a+CD3+肺免疫细胞的比例降低。我们的研究强调，BPD双重打击模型中的围产期肺部炎症会导致与肺部T细胞受体信号通路相关的基因的短期和长期失调，这可能导致儿童中与环境病原体相关的呼吸道疾病增加。和成人BPD。在由绒毛膜炎和出生后高氧诱导的BPD的病理相关的双重打击模型中，我们确定了肺免疫细胞特异性转录组学变化，并表明T细胞受体信号传导基因在短期和长期内下调。这是第一个全面的报告，描绘了转录组的变化，居民的免疫细胞的肺在一个预防相关的双重打击模型的BPD。我们的研究确定了新的常驻肺免疫细胞特异性靶点，用于潜在的治疗调节，以改善BPD早产儿的短期和长期呼吸健康。
Preterm infants with bronchopulmonary dysplasia (BPD) have lifelong increased risk of respiratory morbidities associated with environmental pathogen exposure and underlying mechanisms are poorly understood. The resident immune cells of the lung play vital roles in host defense. However, the effect of perinatal events associated with BPD on pulmonary-specific immune cells is not well understood. We used a double-hit model of BPD induced by prenatal chorioamnionitis followed by postnatal hyperoxia, and performed a global transcriptome analysis of all resident pulmonary immune cells. We show significant up-regulation of genes involved in chemokine-mediated signaling and immune cell chemotaxis, and down-regulation of genes involved in multiple T lymphocyte functions. Multiple genes involved in T cell receptor signaling are downregulated and Cd8a gene expression remains downregulated at 2 months of age in spite of recovery in normoxia for 6 weeks. Furthermore, the proportion of CD8a+CD3+ pulmonary immune cells is decreased. Our study has highlighted that perinatal lung inflammation in a double-hit model of BPD results in short- and long-term dysregulation of genes associated with the pulmonary T cell receptor signaling pathway, which may contribute to increased environmental pathogen-associated respiratory morbidities seen in children and adults with BPD. In a translationally relevant double-hit model of BPD induced by chorioamnionitis and postnatal hyperoxia, we identified pulmonary immune cell-specific transcriptomic changes and showed that T cell receptor signaling genes are downregulated in short term and long term. This is the first comprehensive report delineating transcriptomic changes in resident immune cells of the lung in a translationally relevant double-hit model of BPD. Our study identifies novel resident pulmonary immune cell-specific targets for potential therapeutic modulation to improve short- and long-term respiratory health of preterm infants with BPD.
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DOI：
10.4049/jimmunol.1300270
发表时间：
2013-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kallapur SG;Presicce P;Senthamaraikannan P;Alvarez M;Tarantal AF;Miller LM;Jobe AH;Chougnet CA
通讯作者：
Chougnet CA
影响因子：
64.5
作者：
Olin A;Henckel E;Chen Y;Lakshmikanth T;Pou C;Mikes J;Gustafsson A;Bernhardsson AK;Zhang C;Bohlin K;Brodin P
通讯作者：
Brodin P
DOI：
10.1126/science.1257530
发表时间：
2014-10-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iijima N;Iwasaki A
通讯作者：
Iwasaki A
COVID-19 患者支气管肺泡免疫细胞的单细胞景观。
影响因子：
82.9
作者：
Liao, Mingfeng;Liu, Yang;Zhang, Zheng
通讯作者：
Zhang, Zheng
影响因子：
1.7
作者：
Dedja, Arben;Gucciardi, Antonina;Zaramella, Patrizia
通讯作者：
Zaramella, Patrizia