Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity
Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity
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DOI：
10.1172/jci144734
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发表时间：
2021-03-15
影响因子：
15.9
通讯作者：
Smed-Sorensen, Anna
中科院分区：
文献类型：
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作者：
Falck-Jones, Sara;Vangeti, Sindhu;Smed-Sorensen, Anna
2019冠状病毒病（COVID-19）的免疫病理仍然是谜，导致免疫失调和T细胞淋巴细胞减少。单核细胞髓源性抑制细胞（M-MDSCs）是在炎症条件下扩增的T细胞抑制细胞，但它们在急性呼吸道感染中的作用尚不清楚。我们研究了不同疾病严重程度的COVID-19患者在多个时间点的血液和气道。与健康对照组相比，COVID-19患者血液中的M-MDSC频率升高，但鼻咽或气管内吸入物中的M-MDSC频率未升高。从COVID-19患者中分离的M-MDSCs部分通过精氨酸酶1依赖（arg -1依赖）机制抑制T细胞增殖和ifn - γ产生。此外，患者血浆中Arg-1和IL-6水平升高。COVID-19患者T细胞减少，CD3 zeta链表达下调。序数回归显示，早期M-MDSC频率预测随后的疾病严重程度。总之，M-MDSCs在COVID-19患者血液中扩增，抑制T细胞，并与疾病严重程度密切相关，表明M-MDSCs在失调的COVID-19免疫反应中发挥作用。
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.