tetano
Editor, Senior Moderator
Sci Immunol
. 2021 Feb 23;6(56):eabf6692.
doi: 10.1126/sciimmunol.abf6692.
Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients
Yu Zhao[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Christoph Kilian[SUP] #[/SUP][SUP] 1 [/SUP], Jan-Eric Turner[SUP] #[/SUP][SUP] 3 5 [/SUP], Lidia Bosurgi[SUP] #[/SUP][SUP] 6 7 [/SUP], Kevin Roedl[SUP] #[/SUP][SUP] 8 [/SUP], Patricia Bartsch[SUP] 1 [/SUP], Ann-Christin Gnirck[SUP] 3 5 [/SUP], Filippo Cortesi[SUP] 6 [/SUP], Christoph Schulthei?[SUP] 9 [/SUP], Malte Hellmig[SUP] 1 [/SUP], Leon U B Enk[SUP] 1 [/SUP], Fabian Hausmann[SUP] 2 [/SUP], Alina Borchers[SUP] 1 [/SUP], Milagros N Wong[SUP] 5 [/SUP], Hans-Joachim Paust[SUP] 1 [/SUP], Francesco Siracusa[SUP] 6 [/SUP], Nicola Scheibel[SUP] 6 [/SUP], Marissa Herrmann[SUP] 6 [/SUP], Elisa Rosati[SUP] 10 [/SUP], Petra Bacher[SUP] 10 11 [/SUP], Dominik Kylies[SUP] 3 [/SUP], Dominik Jarczak[SUP] 8 [/SUP], Marc L?tgehetmann[SUP] 12 [/SUP], Susanne Pfefferle[SUP] 12 [/SUP], Stefan Steurer[SUP] 13 [/SUP], Julian Schulze Zur-Wiesch[SUP] 6 [/SUP], Victor G Puelles[SUP] 5 [/SUP], Jan-Peter Sperhake[SUP] 14 [/SUP], Marylyn M Addo[SUP] 15 16 [/SUP], Ansgar W Lohse[SUP] 6 [/SUP], Mascha Binder[SUP] 9 [/SUP], Samuel Huber[SUP] 3 6 [/SUP], Tobias B Huber[SUP] 3 5 [/SUP], Stefan Kluge[SUP] 8 [/SUP], Stefan Bonn[SUP] 2 3 4 [/SUP], Ulf Panzer[SUP] 1 3 [/SUP], Nicola Gagliani[SUP] 17 6 18 19 [/SUP], Christian F Krebs[SUP] 20 3 [/SUP]
Affiliations
Abstract
Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) 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 COVID-19 patients with severe disease and bacterial pneumonia patients 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 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[SUP]+[/SUP] T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients 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.
. 2021 Feb 23;6(56):eabf6692.
doi: 10.1126/sciimmunol.abf6692.
Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients
Yu Zhao[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Christoph Kilian[SUP] #[/SUP][SUP] 1 [/SUP], Jan-Eric Turner[SUP] #[/SUP][SUP] 3 5 [/SUP], Lidia Bosurgi[SUP] #[/SUP][SUP] 6 7 [/SUP], Kevin Roedl[SUP] #[/SUP][SUP] 8 [/SUP], Patricia Bartsch[SUP] 1 [/SUP], Ann-Christin Gnirck[SUP] 3 5 [/SUP], Filippo Cortesi[SUP] 6 [/SUP], Christoph Schulthei?[SUP] 9 [/SUP], Malte Hellmig[SUP] 1 [/SUP], Leon U B Enk[SUP] 1 [/SUP], Fabian Hausmann[SUP] 2 [/SUP], Alina Borchers[SUP] 1 [/SUP], Milagros N Wong[SUP] 5 [/SUP], Hans-Joachim Paust[SUP] 1 [/SUP], Francesco Siracusa[SUP] 6 [/SUP], Nicola Scheibel[SUP] 6 [/SUP], Marissa Herrmann[SUP] 6 [/SUP], Elisa Rosati[SUP] 10 [/SUP], Petra Bacher[SUP] 10 11 [/SUP], Dominik Kylies[SUP] 3 [/SUP], Dominik Jarczak[SUP] 8 [/SUP], Marc L?tgehetmann[SUP] 12 [/SUP], Susanne Pfefferle[SUP] 12 [/SUP], Stefan Steurer[SUP] 13 [/SUP], Julian Schulze Zur-Wiesch[SUP] 6 [/SUP], Victor G Puelles[SUP] 5 [/SUP], Jan-Peter Sperhake[SUP] 14 [/SUP], Marylyn M Addo[SUP] 15 16 [/SUP], Ansgar W Lohse[SUP] 6 [/SUP], Mascha Binder[SUP] 9 [/SUP], Samuel Huber[SUP] 3 6 [/SUP], Tobias B Huber[SUP] 3 5 [/SUP], Stefan Kluge[SUP] 8 [/SUP], Stefan Bonn[SUP] 2 3 4 [/SUP], Ulf Panzer[SUP] 1 3 [/SUP], Nicola Gagliani[SUP] 17 6 18 19 [/SUP], Christian F Krebs[SUP] 20 3 [/SUP]
Affiliations
- PMID: 33622974
- DOI: 10.1126/sciimmunol.abf6692
Abstract
Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) 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 COVID-19 patients with severe disease and bacterial pneumonia patients 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 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[SUP]+[/SUP] T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients 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.