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1.
Signal Transduct Target Ther ; 6(1): 372, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1493075

ABSTRACT

Varying differentiation of myeloid cells is common in tumors, inflammation, autoimmune diseases, and metabolic diseases. The release of cytokines from myeloid cells is an important driving factor that leads to severe COVID-19 cases and subsequent death. This review briefly summarizes the results of single-cell sequencing of peripheral blood, lung tissue, and cerebrospinal fluid of COVID-19 patients and describes the differentiation trajectory of myeloid cells in patients. Moreover, we describe the function and mechanism of abnormal differentiation of myeloid cells to promote disease progression. Targeting myeloid cell-derived cytokines or checkpoints is essential in developing a combined therapeutic strategy for patients with severe COVID-19.


Subject(s)
COVID-19/immunology , Cell Differentiation/immunology , Cellular Microenvironment/immunology , Myeloid Cells/immunology , SARS-CoV-2/immunology , Animals , COVID-19/therapy , Humans , Myeloid Cells/virology , Single-Cell Analysis
2.
Signal Transduct Target Ther ; 6(1): 328, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1392810

ABSTRACT

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Cellular Microenvironment/immunology , Lung/immunology , Receptors, CXCR3/immunology , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2/immunology , Animals , CD8-Positive T-Lymphocytes/pathology , COVID-19/pathology , Disease Models, Animal , Inflammation/immunology , Inflammation/pathology , Interferon-alpha/immunology , Interleukin-6/immunology , Lung/pathology , Lung/virology , Macaca mulatta , Male
3.
Front Immunol ; 11: 1554, 2020.
Article in English | MEDLINE | ID: covidwho-1194588

ABSTRACT

The RNase T2 family consists of evolutionarily conserved endonucleases that express in many different species, including animals, plants, protozoans, bacteria, and viruses. The main biological roles of these ribonucleases are cleaving or degrading RNA substrates. They preferentially cleave single-stranded RNA molecules between purine and uridine residues to generate two nucleotide fragments with 2'3'-cyclic phosphate adenosine/guanosine terminus and uridine residue, respectively. Accumulating studies have revealed that RNase T2 is critical for the pathophysiology of inflammation and cancer. In this review, we introduce the distribution, structure, and functions of RNase T2, its differential roles in inflammation and cancer, and the perspective for its research and related applications in medicine.


Subject(s)
Disease Susceptibility , Endoribonucleases/genetics , Endoribonucleases/metabolism , Inflammation/etiology , Inflammation/metabolism , Neoplasms/etiology , Neoplasms/metabolism , Animals , Biomarkers , Cellular Microenvironment/immunology , Disease Susceptibility/immunology , Endoribonucleases/chemistry , Humans , Immune System/immunology , Immune System/metabolism , Immunomodulation , Inflammation/pathology , Neoplasms/pathology , Structure-Activity Relationship
4.
J Clin Invest ; 131(4)2021 02 15.
Article in English | MEDLINE | ID: covidwho-1172781

ABSTRACT

Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.


Subject(s)
Aging/immunology , Cellular Microenvironment/immunology , Lung/immunology , Macrophages, Alveolar/immunology , Aging/pathology , Animals , Humans , Lung/pathology , Macrophages, Alveolar/pathology , Mice , Mice, Transgenic , RNA-Seq
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