Innate lymphoid cell composition associates with COVID-19 disease severity
Innate lymphoid cell composition associates with COVID-19 disease severity
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DOI：
10.1101/2020.10.13.20211367
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发表时间：
2020-10
期刊：
影响因子：
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通讯作者：
Marina García;Efthymia Kokkinou;Anna Carrasco García;Tiphaine Parrot;L. M. Palma Medina;Kimia T. Maleki;W. Christ;Renata Varnaitė;I. Filipovic;H. Ljunggren;N. Björkström;E. Folkesson;O. Rooyackers;L. Eriksson;A. Sönnerborg;S. Aleman;K. Strålin;Sara Gredmark-Russ;J. Klingström;J. Mjösberg
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文献类型：
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作者：
Marina García;Efthymia Kokkinou;Anna Carrasco García;Tiphaine Parrot;L. M. Palma Medina;Kimia T. Maleki;W. Christ;Renata Varnaitė;I. Filipovic;H. Ljunggren;N. Björkström;E. Folkesson;O. Rooyackers;L. Eriksson;A. Sönnerborg;S. Aleman;K. Strålin;Sara Gredmark-Russ;J. Klingström;J. Mjösberg
目的：先天淋巴细胞（ILC）在由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）中的作用尚不清楚。了解COVID-19的免疫反应有助于揭示发病机制和确定治疗靶点。描述COVID-19患者循环ILC的表型分布，并鉴定与COVID-19相关的血清生物标志物、临床标志物和实验室参数相关的ILC表型。研究方法：使用18参数流式细胞术分析了从中度（n=11）和重度（n=12）COVID-19患者以及健康对照供体（n=16）采集的血液样本。使用监督和无监督的方法，我们检查了ILC的激活状态和归巢配置文件。从所有COVID-19患者中获得临床和实验室参数，并使用多重免疫测定法分析血清生物标志物。结果：与健康对照组相比，COVID-19患者的循环中ILC大量消耗。与对照组相比，来自患者的剩余循环ILC显示中度COVID-19患者的ILC 2频率增加，同时ILC前体（ILCp）减少。ILC 2和ILCp显示出活化的表型，具有增加的CD 69表达，而趋化因子受体CXCR 3和CCR 4的表达水平分别在ILC 2和ILCp以及ILC 1中显著改变。COVID-19患者的活化ILC谱与可溶性炎症标志物相关，而ILC亚群的频率与反映疾病严重程度的实验室参数相关。结论：这项研究为ILC在针对SARS-CoV-2的免疫反应中的潜在作用提供了见解，特别是与COVID-19的严重程度有关。
Objectives: The role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unknown. Understanding the immune response in COVID-19 could contribute to unravel the pathogenesis and identification of treatment targets. To describe the phenotypic landscape of circulating ILCs in COVID-19 patients and to identify ILC phenotypes correlated to serum biomarkers, clinical markers, and laboratory parameters relevant in COVID-19. Methods: Blood samples collected from moderately (n=11) and severely ill (n=12) COVID-19 patients as well as healthy control donors (n=16), were analyzed with 18-parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID-19 patients and serum biomarkers were analyzed with multiplex immunoassays. Results: ILCs were largely depleted from the circulation of COVID-19 patients compared with healthy controls. Remaining circulating ILCs from patients revealed increased frequencies of ILC2 in moderate COVID-19, with a concomitant decrease of ILC precursors (ILCp), as compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID-19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity. Conclusion: This study provides insights into the potential role of ILCs in immune responses against SARS-CoV-2, particularly linked to the severity of COVID-19.