期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 131, 期 6, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI144734
关键词
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资金
- Swedish Research Council
- Swedish Heart Lung Foundation
- Bill & Melinda Gates Foundation
- Knut and Alice Wallenberg Foundation
- Karolinska Institutet
The frequency of M-MDSCs is elevated in the blood of patients with COVID-19, suppressing T cells and strongly associated with disease severity.
The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-gamma production partly via an arginase 1-dependent (Arg-1-dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3 zeta chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response.
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