Activation of Intracellular Complement in Lungs of Patients With Severe COVID-19 Disease Decreases T-Cell Activity in the Lungs.
Activation of Intracellular Complement in Lungs of Patients With Severe COVID-19 Disease Decreases T-Cell Activity in the Lungs.
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DOI：
10.3389/fimmu.2021.700705
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发表时间：
2021
影响因子：
7.3
通讯作者：
Mohapatra S
中科院分区：
文献类型：
--
作者：
Howell MC;Green R;McGill AR;Kahlil RM;Dutta R;Mohapatra SS;Mohapatra S
一种新型冠状病毒，即严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)，于 2019 年末出现，其疾病病理包括无症状到严重呼吸窘迫，伴有多器官衰竭，需要机械呼吸机支持。研究发现，SARS-CoV-2 感染会驱动肺细胞内的细胞内补体激活，从而与疾病的严重程度相关。然而，其细胞和分子机制仍不清楚。为了阐明潜在的机制，我们使用 CIBERSORTx 检查了公开的 RNA 测序数据，并进行了独创性路径分析来解决这一知识差距。为了补充这些发现，我们使用生物信息学工具分析公开的 RNA 测序数据，发现补体上调可能导致重症 COVID-19 患者肺部 T 细胞活性下调。因此，旨在调节经典补体和 T 细胞活性的靶向治疗可能有助于减轻 COVID-19 的促炎作用，减少肺部病理，并提高 COVID-19 患者的生存率。
A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019, with disease pathology ranging from asymptomatic to severe respiratory distress with multi-organ failure requiring mechanical ventilator support. It has been found that SARS-CoV-2 infection drives intracellular complement activation in lung cells that tracks with disease severity. However, the cellular and molecular mechanisms responsible remain unclear. To shed light on the potential mechanisms, we examined publicly available RNA-Sequencing data using CIBERSORTx and conducted a Ingenuity Pathway Analysis to address this knowledge gap. In complement to these findings, we used bioinformatics tools to analyze publicly available RNA sequencing data and found that upregulation of complement may be leading to a downregulation of T-cell activity in lungs of severe COVID-19 patients. Thus, targeting treatments aimed at the modulation of classical complement and T-cell activity may help alleviate the proinflammatory effects of COVID-19, reduce lung pathology, and increase the survival of COVID-19 patients.
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影响因子：
24.8
作者：
Yan B;Freiwald T;Chauss D;Wang L;West E;Mirabelli C;Zhang CJ;Nichols EM;Malik N;Gregory R;Bantscheff M;Ghidelli-Disse S;Kolev M;Frum T;Spence JR;Sexton JZ;Alysandratos KD;Kotton DN;Pittaluga S;Bibby J;Niyonzima N;Olson MR;Kordasti S;Portilla D;Wobus CE;Laurence A;Lionakis MS;Kemper C;Afzali B;Kazemian M
通讯作者：
Kazemian M
影响因子：
14.2
作者：
Schroeder, Harry W., Jr.;Cavacini, Lisa
通讯作者：
Cavacini, Lisa
DOI：
10.1073/pnas.2010540117
发表时间：
2020-10-06
影响因子：
11.1
作者：
Holter JC;Pischke SE;de Boer E;Lind A;Jenum S;Holten AR;Tonby K;Barratt-Due A;Sokolova M;Schjalm C;Chaban V;Kolderup A;Tran T;Tollefsrud Gjølberg T;Skeie LG;Hesstvedt L;Ormåsen V;Fevang B;Austad C;Müller KE;Fladeby C;Holberg-Petersen M;Halvorsen B;Müller F;Aukrust P;Dudman S;Ueland T;Andersen JT;Lund-Johansen F;Heggelund L;Dyrhol-Riise AM;Mollnes TE
通讯作者：
Mollnes TE
影响因子：
7.3
作者：
Knoll R;Schultze JL;Schulte-Schrepping J
通讯作者：
Schulte-Schrepping J
DOI：
10.1093/bioinformatics/btt703
发表时间：
2014-02-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Krämer A;Green J;Pollard J Jr;Tugendreich S
通讯作者：
Tugendreich S