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Editor-in-Chief | Since the outbreak of the novel coronavirus pneumonia (COVID-19) at the end of 2019, it has claimed more than 2.
4 million lives worldwide, and the total number of infections has exceeded 110 million.
While promoting vaccination to protect healthy groups, understanding the pathogenesis of critically ill patients is of great significance to the development of new crown drugs and reducing mortality.
After the new coronavirus invades the human body, it can cause a variety of immune cell responses.
The immune system of mild patients will return to normal after the virus is cleared, while the immune system of severe patients is still highly activated after clearing the virus, producing a large number of cytokines, causing strong lung inflammation and tissue damage, and can even cause systemic disease through blood transmission.
Organ failure.
Studies have shown that this cytoinflammatory factor storm involves the interaction of macrophages, neutrophils, T cells and other groups in patients [1,2].
However, in the lungs and peripheral blood of critically ill patients, the detailed mechanism of immune cell interaction remains to be explored.
As the core role of specific immune response, T cells are more worthy of in-depth analysis.
On February 23, 2021, a team from the Center for Translational Immunology and the Center for Biomedical Artificial Intelligence Research at the University of Hamburg Medical School in Germany published an article Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in Science Immunology.
The lungs of severe COVID-19 patients analyzed the T cell immune response of severe COVID-19 patients through single-cell omics.In this work, the research team collected 9 patients with severe new coronary pneumonia and 5 patients with bacterial pneumonia in alveolar fluid (BAL fluid) and blood samples (Blood) (Figure 1), and more than 130,000 were sorted by convection.
Each immune cell performed single cell transcriptome (Single cell RNA-seq) and surface antigen sequencing (CITE-seq).
In addition, the researchers also sequenced the receptor genes of all CD3-positive T cells (TCR-seq).
Single-cell transcriptome can display the expression of each gene in each cell without bias; measuring surface antigen helps to confirm the subtype of each immune cell; and measuring T cell receptor helps to understand which T cells are in the patient's body Specific clonal expansion occurred under the stimulation of viral antigens.
Figure 1: After the study design and patient sample information were integrated and clustered, the researchers obtained a map of the patient's immune cells (Figure 2).
They found that clonally expanded T cells, especially expanded CD4, helper T cells are mainly derived from alveolar fluid rather than blood, and T cells that produce proinflammatory cytokines are also the main source.
In the lungs.
After quantitatively analyzing the clonal expansion of each subtype of T cells in the lungs and comparing the new coronary pneumonia and bacterial pneumonia, they found that some CD4-positive Th17 cell subgroups were specifically cloned in patients with new coronary disease, but in bacteria In patients with pneumonia, there is little amplification in the body.
Further analysis revealed that a small group of Th17 expressed the gene of Tissue resident memory T cell (Tissue resident memory T cell), and that clones of this group of cells were rarely found in the blood of the same patient, revealing the tissue of the same patient Differences between.
The researchers referred to the memory-resident Th17 cells of this type of tissue as Trm17 cells for short.
More interestingly, these Trm17 cells just express some pro-inflammatory cytokines, such as IL17A, IFNG, GM-CSF, etc.
, suggesting its potential pathogenic function. In order to study the interaction between different immune cell groups, the researchers also conducted a ligand-receptor interactome analysis.
The results show that the receptors corresponding to the ligands secreted by the Trm17 cells are expressed in multiple immune cell groups, including Pro-inflammatory Macrophage (Pro-inflammatory Macrophage) and Pro-fibrotic Macrophage (Pro-fibrotic Macrophage) And CD8-positive killer T cells.
These three cell populations have been reported in previous studies to be directly related to the inflammatory storm and tissue damage in patients with new coronary disease [1, 2].
Among them, the core members of Trm17 and fibrotic macrophages are GM-CSF and its receptor.
Figure 2 2: Patient immune cell map and immune cell interaction network diagram.
The research team also tested IL17A and GM-CSF in the blood of patients with new crown at the protein level, and found that their expression levels were higher in critically ill patients In mild patients, it further suggests that the tissue-resident memory Th17 cells play an important role in regulating the immune response to severe neo-coronary disease.
What is more exciting is that the GM-CSF neutralizing antibody research on the new crown treatment conducted by other teams at the same time has achieved preliminary clinical results [3, 4].
In summary, the study systematically compared and analyzed immune cells in the lungs and blood of severely ill patients with new coronary disease using single-cell omics analysis, perfected the complex mechanism of immune regulation of the new coronavirus, and focused on revealing the specific regulatory function of Trm17 cells.
And the value of drug targeting.
Yu Zhao, a doctoral student at the Center for Translational Immunology and the Center for Biomedical Artificial Intelligence Research at the University of Hamburg School of Medicine, Germany, is the first author of the paper, and Professor Nicola Gagliani and Dr.
Christian Krebs are the corresponding authors.
Attached is the video recording and broadcasting of this research on COVID-19 in a lecture given by Zhao Yu, the first author of this study, at the German Federation of Biomedical Scholars on December 6, 2020.
Original link: https://immunology.
sciencemag.
org/content/6/56/eabf6692 Platemaker: 11 References 1.
Liao et al.
, Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19.
Nat Med 26, 842-844 (2020).
2.
Chua et al, COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.
Nat Biotechnol 38, 970-979 (2020).
3.
De Luca et al.
, GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study.
Lancet Rheumatol 2, e465-e473 (2020).
4.
Temesgen et al.
, GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Control Study.
Mayo Clin Proc, (2020).
4 million lives worldwide, and the total number of infections has exceeded 110 million.
While promoting vaccination to protect healthy groups, understanding the pathogenesis of critically ill patients is of great significance to the development of new crown drugs and reducing mortality.
After the new coronavirus invades the human body, it can cause a variety of immune cell responses.
The immune system of mild patients will return to normal after the virus is cleared, while the immune system of severe patients is still highly activated after clearing the virus, producing a large number of cytokines, causing strong lung inflammation and tissue damage, and can even cause systemic disease through blood transmission.
Organ failure.
Studies have shown that this cytoinflammatory factor storm involves the interaction of macrophages, neutrophils, T cells and other groups in patients [1,2].
However, in the lungs and peripheral blood of critically ill patients, the detailed mechanism of immune cell interaction remains to be explored.
As the core role of specific immune response, T cells are more worthy of in-depth analysis.
On February 23, 2021, a team from the Center for Translational Immunology and the Center for Biomedical Artificial Intelligence Research at the University of Hamburg Medical School in Germany published an article Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in Science Immunology.
The lungs of severe COVID-19 patients analyzed the T cell immune response of severe COVID-19 patients through single-cell omics.In this work, the research team collected 9 patients with severe new coronary pneumonia and 5 patients with bacterial pneumonia in alveolar fluid (BAL fluid) and blood samples (Blood) (Figure 1), and more than 130,000 were sorted by convection.
Each immune cell performed single cell transcriptome (Single cell RNA-seq) and surface antigen sequencing (CITE-seq).
In addition, the researchers also sequenced the receptor genes of all CD3-positive T cells (TCR-seq).
Single-cell transcriptome can display the expression of each gene in each cell without bias; measuring surface antigen helps to confirm the subtype of each immune cell; and measuring T cell receptor helps to understand which T cells are in the patient's body Specific clonal expansion occurred under the stimulation of viral antigens.
Figure 1: After the study design and patient sample information were integrated and clustered, the researchers obtained a map of the patient's immune cells (Figure 2).
They found that clonally expanded T cells, especially expanded CD4, helper T cells are mainly derived from alveolar fluid rather than blood, and T cells that produce proinflammatory cytokines are also the main source.
In the lungs.
After quantitatively analyzing the clonal expansion of each subtype of T cells in the lungs and comparing the new coronary pneumonia and bacterial pneumonia, they found that some CD4-positive Th17 cell subgroups were specifically cloned in patients with new coronary disease, but in bacteria In patients with pneumonia, there is little amplification in the body.
Further analysis revealed that a small group of Th17 expressed the gene of Tissue resident memory T cell (Tissue resident memory T cell), and that clones of this group of cells were rarely found in the blood of the same patient, revealing the tissue of the same patient Differences between.
The researchers referred to the memory-resident Th17 cells of this type of tissue as Trm17 cells for short.
More interestingly, these Trm17 cells just express some pro-inflammatory cytokines, such as IL17A, IFNG, GM-CSF, etc.
, suggesting its potential pathogenic function. In order to study the interaction between different immune cell groups, the researchers also conducted a ligand-receptor interactome analysis.
The results show that the receptors corresponding to the ligands secreted by the Trm17 cells are expressed in multiple immune cell groups, including Pro-inflammatory Macrophage (Pro-inflammatory Macrophage) and Pro-fibrotic Macrophage (Pro-fibrotic Macrophage) And CD8-positive killer T cells.
These three cell populations have been reported in previous studies to be directly related to the inflammatory storm and tissue damage in patients with new coronary disease [1, 2].
Among them, the core members of Trm17 and fibrotic macrophages are GM-CSF and its receptor.
Figure 2 2: Patient immune cell map and immune cell interaction network diagram.
The research team also tested IL17A and GM-CSF in the blood of patients with new crown at the protein level, and found that their expression levels were higher in critically ill patients In mild patients, it further suggests that the tissue-resident memory Th17 cells play an important role in regulating the immune response to severe neo-coronary disease.
What is more exciting is that the GM-CSF neutralizing antibody research on the new crown treatment conducted by other teams at the same time has achieved preliminary clinical results [3, 4].
In summary, the study systematically compared and analyzed immune cells in the lungs and blood of severely ill patients with new coronary disease using single-cell omics analysis, perfected the complex mechanism of immune regulation of the new coronavirus, and focused on revealing the specific regulatory function of Trm17 cells.
And the value of drug targeting.
Yu Zhao, a doctoral student at the Center for Translational Immunology and the Center for Biomedical Artificial Intelligence Research at the University of Hamburg School of Medicine, Germany, is the first author of the paper, and Professor Nicola Gagliani and Dr.
Christian Krebs are the corresponding authors.
Attached is the video recording and broadcasting of this research on COVID-19 in a lecture given by Zhao Yu, the first author of this study, at the German Federation of Biomedical Scholars on December 6, 2020.
Original link: https://immunology.
sciencemag.
org/content/6/56/eabf6692 Platemaker: 11 References 1.
Liao et al.
, Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19.
Nat Med 26, 842-844 (2020).
2.
Chua et al, COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.
Nat Biotechnol 38, 970-979 (2020).
3.
De Luca et al.
, GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study.
Lancet Rheumatol 2, e465-e473 (2020).
4.
Temesgen et al.
, GM-CSF Neutralization With Lenzilumab in Severe COVID-19 Pneumonia: A Case-Control Study.
Mayo Clin Proc, (2020).
