RESUMEN
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Envejecimiento , Genética , Alergia e Inmunología , Betacoronavirus , Linfocitos T CD4-Positivos , Metabolismo , Linaje de la Célula , Ensamble y Desensamble de Cromatina , Infecciones por Coronavirus , Alergia e Inmunología , Síndrome de Liberación de Citoquinas , Alergia e Inmunología , Citocinas , Genética , Susceptibilidad a Enfermedades , Citometría de Flujo , Métodos , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Reordenamiento Génico , Sistema Inmunológico , Biología Celular , Alergia e Inmunología , Inmunocompetencia , Genética , Inflamación , Genética , Alergia e Inmunología , Espectrometría de Masas , Métodos , Pandemias , Neumonía Viral , Alergia e Inmunología , Análisis de Secuencia de ARN , Análisis de la Célula Individual , TranscriptomaRESUMEN
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Envejecimiento , Genética , Alergia e Inmunología , Betacoronavirus , Linfocitos T CD4-Positivos , Metabolismo , Linaje de la Célula , Ensamble y Desensamble de Cromatina , Infecciones por Coronavirus , Alergia e Inmunología , Síndrome de Liberación de Citoquinas , Alergia e Inmunología , Citocinas , Genética , Susceptibilidad a Enfermedades , Citometría de Flujo , Métodos , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Reordenamiento Génico , Sistema Inmunológico , Biología Celular , Alergia e Inmunología , Inmunocompetencia , Genética , Inflamación , Genética , Alergia e Inmunología , Espectrometría de Masas , Métodos , Pandemias , Neumonía Viral , Alergia e Inmunología , Análisis de Secuencia de ARN , Análisis de la Célula Individual , TranscriptomaRESUMEN
Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Envejecimiento , Genética , Alergia e Inmunología , Betacoronavirus , Linfocitos T CD4-Positivos , Metabolismo , Linaje de la Célula , Ensamble y Desensamble de Cromatina , Infecciones por Coronavirus , Alergia e Inmunología , Síndrome de Liberación de Citoquinas , Alergia e Inmunología , Citocinas , Genética , Susceptibilidad a Enfermedades , Citometría de Flujo , Métodos , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Reordenamiento Génico , Sistema Inmunológico , Biología Celular , Alergia e Inmunología , Inmunocompetencia , Genética , Inflamación , Genética , Alergia e Inmunología , Espectrometría de Masas , Métodos , Pandemias , Neumonía Viral , Alergia e Inmunología , Análisis de Secuencia de ARN , Análisis de la Célula Individual , TranscriptomaRESUMEN
<p><b>OBJECTIVE</b>To identify ubiquitinated proteins from complex human multiple myeloma (MM) U266 cells, a malignant disorder of differentiated human B cells.</p><p><b>METHODS</b>Employing a globally proteomic strategy combining of immunoprecipitation, LC-MS/MS and SCX-LC-MS analysis to identified ubiquitination sites, which were identified by detecting signature peptides containing a GG-tag (114.1 Da) and an LRGG-tag (383.2 Da).</p><p><b>RESULTS</b>In total, 52 ubiquitinated proteins containing 73 ubiquitination sites of which 14 and 59 sites contained LRGG-tag and GG-tag were identified, respectively.</p><p><b>CONCLUSION</b>Classification analysis by of the proteins identified in the study based on the PANTHER showed that they were associated with multiple functional groups. This suggested the involvement of many endogenous proteins in the ubiquitination in MM.</p>