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

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; Schulze zur Wiesch, Julian; 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.

Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome 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 patients with severe COVID-19 and patients with bacterial pneumonia not associated with viral infection. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like T(H)17 cells (T(RM)17 cells) in the lungs even after viral clearance. These T(RM)17 cells were characterized by a potentially pathogenic cytokine expression profile of IL17A and CSF2 (GM-CSF). Interactome analysis suggests that T(RM)17 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 patients with COVID-19 were associated with a more severe clinical course. Collectively, our study suggests that pulmonary T(RM)17 cells are one potential orchestrator of the hyperinflammation in severe COVID-19.