García Marina, Kokkinou Efthymia, Carrasco García Anna, Parrot Tiphaine, Palma Medina Laura M, Maleki Kimia T, Christ Wanda, Varnaitė Renata, Filipovic Iva, Ljunggren Hans-Gustaf, Björkström Niklas K, Folkesson Elin, Rooyackers Olav, Eriksson Lars I, Sönnerborg Anders, Aleman Soo, Strålin Kristoffer, Gredmark-Russ Sara, Klingström Jonas, Mjösberg Jenny
Department of Medicine Huddinge Center for Infectious Medicine Karolinska Institutet Karolinska University Hospital Stockholm Sweden.
Department of Infectious Diseases Karolinska University Hospital Stockholm Sweden.
Clin Transl Immunology. 2020 Dec 14;9(12):e1224. doi: 10.1002/cti2.1224. eCollection 2020.
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. Here, we describe the phenotypic landscape of circulating ILCs in COVID-19 patients and identified ILC phenotypes correlated to serum biomarkers, clinical markers and laboratory parameters relevant in COVID-19.
Blood samples collected from moderately ( = 11) and severely ill ( = 12) COVID-19 patients, as well as healthy control donors ( = 16), were analysed 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 analysed with multiplex immunoassays.
Innate lymphoid cells were largely depleted from the circulation of COVID-19 patients compared with healthy controls. Remaining circulating ILCs revealed decreased frequencies of ILC2 in severe COVID-19, with a concomitant decrease of ILC precursors (ILCp) in all patients, 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.
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.
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，固有淋巴细胞（ILC）的作用尚不清楚。了解COVID-19中的免疫反应有助于阐明其发病机制并确定治疗靶点。在此，我们描述了COVID-19患者循环ILC的表型特征，并确定了与COVID-19相关的血清生物标志物、临床指标和实验室参数相关的ILC表型。
采用18参数流式细胞术分析从中度（n = 11）和重度（n = 12）COVID-19患者以及健康对照者（n = 16）采集的血样。使用监督和非监督方法，我们检查了ILC的激活状态和归巢特征。从所有COVID-19患者中获取临床和实验室参数，并通过多重免疫测定分析血清生物标志物。
与健康对照相比，COVID-19患者循环中的固有淋巴细胞大量减少。与对照组相比，重度COVID-19患者中剩余的循环ILC显示ILC2频率降低，所有患者的ILC前体（ILCp）均随之减少。ILC2和ILCp表现出激活的表型，CD69表达增加，而趋化因子受体CXCR3和CCR4的表达水平在ILC2和ILCp以及ILC1中分别发生了显著变化。COVID-19患者的激活ILC特征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。
本研究深入探讨了ILC在针对SARS-CoV-2的免疫反应中的潜在作用，特别是与COVID-19的严重程度相关。
