1. Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients
- Author
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Yu, Zhao, Christoph, Kilian, Jan-Eric, Turner, Lidia, Bosurgi, Kevin, Roedl, Patricia, Bartsch, Ann-Christin, Gnirck, Filippo, Cortesi, Christoph, Schultheiß, Malte, Hellmig, Leon U B, Enk, Fabian, Hausmann, Alina, Borchers, Milagros N, Wong, Hans-Joachim, Paust, Francesco, Siracusa, Nicola, Scheibel, Marissa, Herrmann, Elisa, Rosati, Petra, Bacher, Dominik, Kylies, Dominik, Jarczak, Marc, Lütgehetmann, Susanne, Pfefferle, Stefan, Steurer, Julian Schulze, Zur-Wiesch, Victor G, Puelles, Jan-Peter, Sperhake, Marylyn M, Addo, Ansgar W, Lohse, Mascha, Binder, Samuel, Huber, Tobias B, Huber, Stefan, Kluge, Stefan, Bonn, Ulf, Panzer, Nicola, Gagliani, and Christian F, Krebs
- Subjects
Inflammation ,COVID-19 ,Granulocyte-Macrophage Colony-Stimulating Factor ,Infectious Disease ,macromolecular substances ,respiratory system ,respiratory tract diseases ,Clone Cells ,SciImmunol r-articles ,Coronavirus ,Pneumonia, Bacterial ,Humans ,Th17 Cells ,Cytokines ,Myeloid Cells ,Bronchoalveolar Lavage Fluid ,Immunologic Memory ,Lung ,Research Articles ,Research Article - Abstract
Tissue-resident memory-like TH17 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 (TH17) 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 TH17 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 TH17 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 TH17 cells (TRM17 cells) in the lungs even after viral clearance. These TRM17 cells were characterized by a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that TRM17 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 TRM17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.
- Published
- 2020