Limited TCR repertoire and ENTPD1 dysregulation mark late-stage COVID-19
| Autor: | Marta Vuerich, Ahmadreza Kalbasi, Eric M. Miller, Na Wang, Simon C. Robson, Eva Csizmadia, Ann E. Woolley, Jonathon J. Graham, Zachary Manickas-Hill, Kara Gorman, Maria Serena Longhi, Clément N. David, Jonathan L. Hecht, Shahzad Shaefi |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | iScience iScience, Vol 24, Iss 10, Pp 103205-(2021) |
| ISSN: | 2589-0042 |
| Popis: | T 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. Heightened ENTPD1/CD39 is paralleled by elevations in STAT-3 and HIF-1α transcription factors; and by markedly reduced CD39-antisense-RNA, a long-noncoding-RNA negatively regulating ENTPD1/CD39 at the post-transcriptional level. Limited TCR repertoire and aberrant regulation of ENTPD1/CD39 could have permissive roles in COVID-19 progression and indicate potential therapeutic targets to reverse disease. Graphical abstract Immunology; Virology |
| Databáze: | OpenAIRE |
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