文章基本信息

标题：Limited TCR repertoire and ENTPD1 dysregulation mark late-stage COVID-19
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作者：Na Wang ; Marta Vuerich ; Ahmadreza Kalbasi 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：10
页码：1-16
DOI：10.1016/j.isci.2021.103205
语种：English
出版社：Elsevier
摘要：SummaryT cell exhaustion and dysfunction are hallmarks of severe COVID-19. To gain insights into the pathways underlying these alterations, we performed a comprehensive transcriptome analysis of peripheral-blood-mononuclear-cells (PBMCs), spleen, lung, kidney, liver, and heart obtained at autopsy from COVID-19 patients and matched controls, using the nCounter CAR-T-Characterization panel. We found substantial gene alterations in COVID-19-impacted organs, especially the lung where altered TCR repertoires are noted. Reduced TCR repertoires are also observed in PBMCs of severe COVID-19 patients.ENTPD1/CD39, an ectoenzyme defining exhausted T-cells, is upregulated in the lung, liver, spleen, and PBMCs of severe COVID-19 patients where expression positively correlates with markers of vasculopathy. HeightenedENTPD1/CD39is paralleled by elevations inSTAT-3andHIF-1αtranscription factors; and by markedly reducedCD39-antisense-RNA, a long-noncoding-RNA negatively regulatingENTPD1/CD39at the post-transcriptional level. Limited TCR repertoire and aberrant regulation ofENTPD1/CD39could have permissive roles in COVID-19 progression and indicate potential therapeutic targets to reverse disease.Graphical abstractDisplay OmittedHighlights•Transcriptome profiling of COVID-19 autoptic tissue and PBMC was carried out•There is limited TCR repertoire in lung, kidney and PBMC of severe COVID-19 cases•There are increased CD39 levels in PBMC of severe COVID-19 patients•High HIF-1a and STAT-3 and low CD39-antisense might be linked with CD39 increaseImmunology; Virology