We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Clonal expansion and activation of tissue-resident memory-like T<sub>H</sub>17 cells expressing GM-CSF in the lungs of patients with severe COVID-19.
- Authors
Zhao, Yu; Kilian, Christoph; Turner, Jan-Eric; Bosurgi, Lidia; Roedl, Kevin; Bartsch, Patricia; Gnirck, Ann-Christin; Cortesi, Filippo; Schultheiß, Christoph; Hellmig, Malte; Enk, Leon U.B.; Hausmann, Fabian; Borchers, Alina; Wong, Milagros N.; Paust, Hans-Joachim; Siracusa, Francesco; Scheibel, Nicola; Herrmann, Marissa; Rosati, Elisa; Bacher, Petra
- Abstract
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.
- Publication
Science Immunology, 2021, Vol 6, Issue 56, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abf6692