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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

Authors: 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.

Online: https://immunology.sciencemag.org/lookup/doi/10.1126/sciimmunol.abf6692

Issue: Sci Immunol . 2021 Feb 23;6(56):eabf6692.


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.