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Science immunology
02 23, 2021;6 (56):

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

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, Christian F Krebs
Author Information
  1. Yu Zhao: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  2. Christoph Kilian: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  3. Jan-Eric Turner: Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Germany.
  4. Lidia Bosurgi: I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.
  5. Kevin Roedl: Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  6. Patricia Bartsch: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  7. Ann-Christin Gnirck: Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Germany.
  8. Filippo Cortesi: I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  9. Christoph Schultheiß: Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany. ORCID
  10. Malte Hellmig: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  11. Leon U B Enk: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  12. Fabian Hausmann: Institute of Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  13. Alina Borchers: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany.
  14. Milagros N Wong: III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.
  15. Hans-Joachim Paust: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany.
  16. Francesco Siracusa: I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.
  17. Nicola Scheibel: I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  18. Marissa Herrmann: I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  19. Elisa Rosati: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
  20. Petra Bacher: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
  21. Dominik Kylies: Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Germany.
  22. Dominik Jarczak: Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  23. Marc Lütgehetmann: Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  24. Susanne Pfefferle: Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  25. Stefan Steurer: Institute for Pathology, University Medical Center Hamburg-Eppendorf, Germany.
  26. Julian Schulze Zur-Wiesch: I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  27. Victor G Puelles: III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  28. Jan-Peter Sperhake: Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, Germany.
  29. Marylyn M Addo: I. Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  30. Ansgar W Lohse: I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.
  31. Mascha Binder: Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
  32. Samuel Huber: Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Germany. ORCID
  33. Tobias B Huber: Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Germany. ORCID
  34. Stefan Kluge: Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Germany.
  35. Stefan Bonn: Institute of Medical Systems Biology, University Medical Center Hamburg-Eppendorf, Germany. ORCID
  36. Ulf Panzer: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany.
  37. Nicola Gagliani: Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Germany. n.gagliani@uke.de c.krebs@uke.de. ORCID
  38. Christian F Krebs: III. Department of Medicine, Division of Translational Immunology, University Medical Center Hamburg-Eppendorf, Germany. n.gagliani@uke.de c.krebs@uke.de. ORCID
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 and (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.

References

  1. Nat Rev Immunol. 2017 Sep;17(9):535-544 [PMID: 28555673]
  2. Nat Commun. 2019 Dec 4;10(1):5531 [PMID: 31797935]
  3. Cell. 2020 Nov 25;183(5):1340-1353.e16 [PMID: 33096020]
  4. Nat Rev Immunol. 2020 Sep;20(9):529-536 [PMID: 32728222]
  5. Cell Host Microbe. 2020 Jul 8;28(1):117-123.e1 [PMID: 32411313]
  6. PLoS Pathog. 2016 Jun 23;12(6):e1005624 [PMID: 27337042]
  7. Nat Med. 2020 Jul;26(7):1070-1076 [PMID: 32514174]
  8. Lancet. 2020 Feb 15;395(10223):497-506 [PMID: 31986264]
  9. Cell Rep. 2016 Jul 12;16(2):392-404 [PMID: 27346359]
  10. N Engl J Med. 2021 Jan 7;384(1):20-30 [PMID: 33332779]
  11. N Engl J Med. 2021 Feb 25;384(8):693-704 [PMID: 32678530]
  12. Nat Rev Immunol. 2016 Mar;16(3):149-63 [PMID: 26875830]
  13. Nat Rev Immunol. 2020 Jun;20(6):345-346 [PMID: 32358580]
  14. Cell Rep. 2017 Sep 19;20(12):2921-2934 [PMID: 28930685]
  15. Cell. 2019 Aug 22;178(5):1176-1188.e15 [PMID: 31442406]
  16. Nat Med. 2020 Jun;26(6):842-844 [PMID: 32398875]
  17. N Engl J Med. 2020 Apr 30;382(18):1708-1720 [PMID: 32109013]
  18. Med Klin Intensivmed Notfmed. 2020 Dec;115(Suppl 3):111-114 [PMID: 32291505]
  19. Lancet Rheumatol. 2020 Aug;2(8):e457-ee458 [PMID: 32835251]
  20. Cold Spring Harb Perspect Biol. 2018 Mar 1;10(3): [PMID: 28432133]
  21. J Exp Med. 2015 May 4;212(5):681-97 [PMID: 25897174]
  22. Immunity. 2016 Nov 15;45(5):963-973 [PMID: 27851925]
  23. Sci Immunol. 2020 Aug 7;5(50): [PMID: 32769171]
  24. F1000Res. 2020 Jan 27;9:47 [PMID: 32789006]
  25. J Exp Med. 2016 Sep 19;213(10):1983-98 [PMID: 27595596]
  26. Immunity. 2020 Aug 18;53(2):442-455.e4 [PMID: 32668194]
  27. Immunity. 2020 Dec 15;53(6):1258-1271.e5 [PMID: 33296686]
  28. Lancet Infect Dis. 2020 May;20(5):533-534 [PMID: 32087114]
  29. N Engl J Med. 2020 Dec 10;383(24):2333-2344 [PMID: 33085857]
  30. Lancet Respir Med. 2020 Aug;8(8):822-830 [PMID: 32559419]
  31. Lancet Rheumatol. 2020 Jul;2(7):e393-e400 [PMID: 32835245]
  32. J Exp Med. 2019 Sep 2;216(9):2184-2201 [PMID: 31289116]
  33. J Exp Med. 2020 Jan 6;217(1): [PMID: 31611249]
  34. Cell. 2019 Jun 13;177(7):1888-1902.e21 [PMID: 31178118]
  35. Immunity. 2015 Sep 15;43(3):554-65 [PMID: 26297566]
  36. Nature. 2021 Feb;590(7847):635-641 [PMID: 33429418]
  37. Natl Sci Rev. 2020 Jun;7(6):998-1002 [PMID: 34676125]
  38. Nat Biotechnol. 2020 Aug;38(8):970-979 [PMID: 32591762]
  39. Nat Rev Immunol. 2020 Aug;20(8):507-514 [PMID: 32576980]
  40. J Mol Diagn. 2012 Jan;14(1):22-9 [PMID: 22166544]
  41. Lancet Rheumatol. 2020 Aug;2(8):e465-e473 [PMID: 32835256]
  42. Life Sci Alliance. 2020 Jun 22;3(8): [PMID: 32571802]
  43. Mayo Clin Proc. 2020 Nov;95(11):2382-2394 [PMID: 33153629]
  44. Nat Protoc. 2020 Apr;15(4):1484-1506 [PMID: 32103204]
  45. Nat Med. 2012 Jul 06;18(7):1028-40 [PMID: 22772564]
  46. Nature. 2012 Apr 26;484(7395):514-8 [PMID: 22466287]

MeSH Term

Bronchoalveolar Lavage Fluid
COVID-19
Clone Cells
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Immunologic Memory
Inflammation
Lung
Myeloid Cells
Pneumonia, Bacterial
Th17 Cells

Chemicals

Granulocyte-Macrophage Colony-Stimulating Factor
Journal Article Research Support, Non-U.S. Gov't

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