Functional myeloid-derived suppressor cells expand in blood but not airways of COVID-19 patients and predict disease severity
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Falck-Jones S, Vangeti S, Yu M, Falck-Jones R, Cagigi A, Badolati I, Osterberg B, Lautenbach MJ, Ahlberg E, Lin A, Szurgot I, Lenart K, Hellgren F, Salde J, Albert J, Johansson N, Bell M, Lore K, Farnert A, Smed-Sorensen A
J Clin Invest 131 (6) -
[2021-01-28; online 2021-01-25]
The immunopathology of COVID-19 remains enigmatic, exhibiting immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSC) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied blood and airways of COVID-19 patients across disease severity at multiple timepoints. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of COVID-19 patients compared to controls. M-MDSCs isolated from COVID-19 patients suppressed T cell proliferation and IFNγ production partly via an arginase-1 (Arg-1) dependent mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. COVID-19 patients had fewer T cells, and displayed downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expand in blood of COVID-19 patients, suppress T cells and strongly associate with disease severity, suggesting a role for M-MDSCs in the dysregulated COVID-19 immune response.
Funder: KAW/SciLifeLab National COVID program
Research Area: High-throughput and high-content serology
PubMed 33492309
DOI 10.1172/JCI144734
Crossref 10.1172/JCI144734
NA: Available on request