Tissue-resident memory-like T H 17 cells are clonally expanded in bronchoalveolar lavage fluid of patients with severe COVID-19. TH17 cells in severe COVID-19 Generation of T helper 17 (T H 17) cells has been associated with immunopathogenesis in multiple autoimmune diseases. Using integrated single-cell transcriptome and TCR repertoire profiling, Zhao et al . showed that a population of T H 17 cells with features of tissue-resident memory T cells was clonally expanded in bronchoalveolar lavage (BAL) fluid collected from the lungs of patients with severe COVID-19, but not in samples from patients with bacterial pneumonia. Lung tissue–resident memory-like T H 17 cells were the primary immune cell type in BAL expressing the cytokine GM-CSF, which was also elevated in serum from a cohort of patients with severe COVID-19 compared with those with moderate disease. These results provide insight into specific T cell responses associated with severe COVID-19 pneumonia and identify a potential cellular target of GM-CSF–neutralizing therapies. Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome with high mortality in patients with severe coronavirus disease 2019 (COVID-19). To understand the underlying mechanisms involved in lung pathology, we investigated the role of the lung-specific immune response. We profiled immune cells in bronchoalveolar lavage fluid and blood collected from patients with severe COVID-19 and patients with bacterial pneumonia not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like T H 17 cells (T RM 17 cells) in the lungs even after viral clearance. These T RM 17 cells were characterized by a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that T RM 17 cells can interact with lung macrophages and cytotoxic CD8 + T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of patients with COVID-19 were associated with a more severe clinical course. Collectively, our study suggests that pulmonary T RM 17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.
【초록키워드】 COVID-19, coronavirus disease, Transcriptome, Macrophage, Respiratory distress syndrome, viral infection, Coronavirus disease 2019, Severe COVID-19 pneumonia, COVID-19 pneumonia, immune response, macrophages, IL-17A, severe COVID-19, acute respiratory distress syndrome, Pneumonia, T cells, GM-CSF, disease severity, lung, cytokine, Lung injury, CD8, viral clearance, BAL, serum, Cohort, T cell, Clinical course, Viral, Bronchoalveolar lavage fluid, cells, hyperinflammation, Lungs, Immunopathogenesis, Patient, immune cells, interactome, bacterial pneumonia, Autoimmune diseases, TCR, mechanism, single-cell, T cell response, memory T cell, Blood, Therapies, Bacterial, Lung pathology, acute respiratory distress, cellular, Bronchoalveolar lavage, Analysis, Immune cell, lung damage, cell type, respiratory distress, T helper, Th17 cells, tissues, moderate disease, severe coronavirus disease, syndrome, high mortality, lung tissue, pathogenic, IL17A, protein level, CSF2, clone, helper, Generation, feature, Cell, pulmonary T, identify, collected, involved, subsequent, investigated, elevated, characterized, contribute, expressing, cohort of patient, cytokine expression profile, immune cell type, patients with COVID-19, 【제목키워드】 lung, Patient, clonal expansion, Activation, Cell, expressing,