1. Dysregulation of the leukocyte signaling landscape during acute COVID-19.
- Author
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Turnbull, Isaiah R., Fuchs, Anja, Remy, Kenneth E., Kelly, Michael P., Frazier, Elfaridah P., Ghosh, Sarbani, Chang, Shin-Wen, Mazer, Monty B., Hess, Annie, Leonard, Jennifer M., Hoofnagle, Mark H., Colonna, Marco, and Hotchkiss, Richard S.
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T cells , *COVID-19 pandemic , *COVID-19 , *LEUCOCYTES , *MONOCYTES , *MYELOID cells , *CELL populations - Abstract
The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation was tightly correlated with circulating IL-6 levels and high levels of phospho-STAT3 was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-γ production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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