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Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients

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Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients. / 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; Kylies, Dominik; Jarczak, Dominik; Lütgehetmann, Marc; Pfefferle, Susanne; Steurer, Stefan; Zur Wiesch, Julian Schulze; Puelles, Victor G.; Sperhake, Jan Peter; Addo, Marylyn M.; Lohse, Ansgar W.; Binder, Mascha; Huber, Samuel; Huber, Tobias B.; Kluge, Stefan; Bonn, Stefan; Panzer, Ulf; Gagliani, Nicola; Krebs, Christian F.

In: SCI IMMUNOL, Vol. 6, No. 56, eabf6692, 23.02.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Zhao, Y, Kilian, C, Turner, JE, Bosurgi, L, Roedl, K, Bartsch, P, Gnirck, AC, Cortesi, F, Schultheiß, C, Hellmig, M, Enk, LUB, Hausmann, F, Borchers, A, Wong, MN, Paust, HJ, Siracusa, F, Scheibel, N, Herrmann, M, Rosati, E, Bacher, P, Kylies, D, Jarczak, D, Lütgehetmann, M, Pfefferle, S, Steurer, S, Zur Wiesch, JS, Puelles, VG, Sperhake, JP, Addo, MM, Lohse, AW, Binder, M, Huber, S, Huber, TB, Kluge, S, Bonn, S, Panzer, U, Gagliani, N & Krebs, CF 2021, 'Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients', SCI IMMUNOL, vol. 6, no. 56, eabf6692. https://doi.org/10.1126/SCIIMMUNOL.ABF6692, https://doi.org/10.1126/sciimmunol.abf6692

APA

Zhao, Y., Kilian, C., Turner, J. E., Bosurgi, L., Roedl, K., Bartsch, P., Gnirck, A. C., Cortesi, F., Schultheiß, C., Hellmig, M., Enk, L. U. B., Hausmann, F., Borchers, A., Wong, M. N., Paust, H. J., Siracusa, F., Scheibel, N., Herrmann, M., Rosati, E., ... Krebs, C. F. (2021). Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients. SCI IMMUNOL, 6(56), [eabf6692]. https://doi.org/10.1126/SCIIMMUNOL.ABF6692, https://doi.org/10.1126/sciimmunol.abf6692

Vancouver

Zhao Y, Kilian C, Turner JE, Bosurgi L, Roedl K, Bartsch P et al. Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients. SCI IMMUNOL. 2021 Feb 23;6(56). eabf6692. https://doi.org/10.1126/SCIIMMUNOL.ABF6692, https://doi.org/10.1126/sciimmunol.abf6692

Bibtex

@article{2e078d487df34b50a3b1bf07c88df727,
title = "Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients",
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+ 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.",
keywords = "Bronchoalveolar Lavage Fluid/cytology, COVID-19/complications, Clone Cells, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism, Humans, Immunologic Memory, Inflammation/etiology, Lung/immunology, Myeloid Cells, Pneumonia, Bacterial/immunology, Th17 Cells/immunology",
author = "Yu Zhao and Christoph Kilian and Turner, {Jan Eric} and Lidia Bosurgi and Kevin Roedl and Patricia Bartsch and Gnirck, {Ann Christin} and Filippo Cortesi and Christoph Schulthei{\ss} and Malte Hellmig and Enk, {Leon U.B.} and Fabian Hausmann and Alina Borchers and Wong, {Milagros N.} and Paust, {Hans Joachim} and Francesco Siracusa and Nicola Scheibel and Marissa Herrmann and Elisa Rosati and Petra Bacher and Dominik Kylies and Dominik Jarczak and Marc L{\"u}tgehetmann and Susanne Pfefferle and Stefan Steurer and {Zur Wiesch}, {Julian Schulze} and Puelles, {Victor G.} and Sperhake, {Jan Peter} and Addo, {Marylyn M.} and Lohse, {Ansgar W.} and Mascha Binder and Samuel Huber and Huber, {Tobias B.} and Stefan Kluge and Stefan Bonn and Ulf Panzer and Nicola Gagliani and Krebs, {Christian F.}",
note = "Copyright {\textcopyright} 2021, American Association for the Advancement of Science.",
year = "2021",
month = feb,
day = "23",
doi = "10.1126/SCIIMMUNOL.ABF6692",
language = "English",
volume = "6",
journal = "SCI IMMUNOL",
issn = "2470-9468",
publisher = "American Association for the Advancement of Science",
number = "56",

}

RIS

TY - JOUR

T1 - Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients

AU - Zhao, Yu

AU - Kilian, Christoph

AU - Turner, Jan Eric

AU - Bosurgi, Lidia

AU - Roedl, Kevin

AU - Bartsch, Patricia

AU - Gnirck, Ann Christin

AU - Cortesi, Filippo

AU - Schultheiß, Christoph

AU - Hellmig, Malte

AU - Enk, Leon U.B.

AU - Hausmann, Fabian

AU - Borchers, Alina

AU - Wong, Milagros N.

AU - Paust, Hans Joachim

AU - Siracusa, Francesco

AU - Scheibel, Nicola

AU - Herrmann, Marissa

AU - Rosati, Elisa

AU - Bacher, Petra

AU - Kylies, Dominik

AU - Jarczak, Dominik

AU - Lütgehetmann, Marc

AU - Pfefferle, Susanne

AU - Steurer, Stefan

AU - Zur Wiesch, Julian Schulze

AU - Puelles, Victor G.

AU - Sperhake, Jan Peter

AU - Addo, Marylyn M.

AU - Lohse, Ansgar W.

AU - Binder, Mascha

AU - Huber, Samuel

AU - Huber, Tobias B.

AU - Kluge, Stefan

AU - Bonn, Stefan

AU - Panzer, Ulf

AU - Gagliani, Nicola

AU - Krebs, Christian F.

N1 - Copyright © 2021, American Association for the Advancement of Science.

PY - 2021/2/23

Y1 - 2021/2/23

N2 - 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+ 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.

AB - 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+ 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.

KW - Bronchoalveolar Lavage Fluid/cytology

KW - COVID-19/complications

KW - Clone Cells

KW - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism

KW - Humans

KW - Immunologic Memory

KW - Inflammation/etiology

KW - Lung/immunology

KW - Myeloid Cells

KW - Pneumonia, Bacterial/immunology

KW - Th17 Cells/immunology

UR - http://www.scopus.com/inward/record.url?scp=85101934657&partnerID=8YFLogxK

U2 - 10.1126/SCIIMMUNOL.ABF6692

DO - 10.1126/SCIIMMUNOL.ABF6692

M3 - SCORING: Journal article

C2 - 33622974

VL - 6

JO - SCI IMMUNOL

JF - SCI IMMUNOL

SN - 2470-9468

IS - 56

M1 - eabf6692

ER -