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

Media type: E-Article

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

Contributor: Zhao, Yu [Author]; Kilian, Christoph [Author]; Turner, Jan-Eric [Author]; Bosurgi, Lidia [Author]; Roedl, Kevin [Author]; Bartsch, Patricia [Author]; Gnirck, Ann-Christin [Author]; Cortesi, Filippo [Author]; Schultheiß, Christoph [Author]; Hellmig, Malte [Author]; Enk, Leon U. B. [Author]; Hausmann, Fabian [Author]; Borchers, Alina [Author]; Wong, Milagros N. [Author]; Paust, Hans-Joachim [Author]; Siracusa, Francesco [Author]; Scheibel, Nicola [Author]; Herrmann, Marissa [Author]; Rosati, Elisa [Author]; Bacher, Petra [Author]; Kylies, Dominik [Author]; Jarczak, Dominik [Author]; Lütgehetmann, Marc [Author]; Pfefferle, Susanne [Author]; Steurer, Stefan [Author]; Zur-Wiesch, Julian Schulze [Author]; Puelles, Victor G. [Author]; Sperhake, Jan-Peter [Author]; Addo, Marylyn M. [Author]; Lohse, Ansgar W. [Author]; Binder, Mascha [Author]; Huber, Samuel [Author]; Huber, Tobias B. [Author]; Kluge, Stefan [Author]; Bonn, Stefan [Author]; Panzer, Ulf [Author]; Gagliani, Nicola [Author]; Krebs, Christian F. [Author]

Published: 2021

Language: English

DOI: 10.1126/sciimmunol.abf6692

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Description: 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.

Access State: Open Access

Rights information: Attribution (CC BY)

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