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)2021 02 23.
Article
in English
| MEDLINE | ID: covidwho-1099742
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Granulocyte-Macrophage Colony-Stimulating Factor
/
Th17 Cells
/
COVID-19
/
Immunologic Memory
/
Lung
Type of study:
Prognostic study
Topics:
Long Covid
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Sciimmunol.abf6692
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