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

Authors:
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
Year of publication:
2021
Volume:
6
Issue:
56
Issn:
2470-9468
Journal title abbreviated:
Sci Immunol
Journal title long:
Science immunology
Impact factor:
17.727
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 <i>IL17A</i> and <i>CSF2</i> (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.