1. Clonal expansion and activation of tissue-resident memory-like T H 17 cells expressing GM-CSF in the lungs of patients with severe COVID-19
- Author
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Francesco Siracusa, Ansgar W. Lohse, Dominik Kylies, Filippo Cortesi, Yu Zhao, Mascha Binder, Nicola Gagliani, Susanne Pfefferle, Milagros N. Wong, Victor G. Puelles, Marissa Herrmann, Lidia Bosurgi, Christoph Schultheiß, Leon U. B. Enk, Patricia Bartsch, Stefan Bonn, Malte Hellmig, Ulf Panzer, Kevin Roedl, Dominik Jarczak, Elisa Rosati, Samuel Huber, Petra Bacher, Jan-Eric Turner, Christoph Kilian, Christian Krebs, Jan-Peter Sperhake, Ann-Christin Gnirck, Marc Lütgehetmann, Julian Schulze Zur-Wiesch, Stefan Steurer, Alina Borchers, Nicola Scheibel, Stefan Kluge, Marylyn M. Addo, Hans-Joachim Paust, Tobias B. Huber, and Fabian Hausmann
- Subjects
0301 basic medicine ,ARDS ,Lung ,medicine.diagnostic_test ,business.industry ,T cell ,Immunology ,General Medicine ,Lung injury ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Granulocyte macrophage colony-stimulating factor ,Bronchoalveolar lavage ,medicine.anatomical_structure ,Immune system ,030220 oncology & carcinogenesis ,medicine ,Cytotoxic T cell ,business ,medicine.drug - 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.
- Published
- 2021