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

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Sci Immunol


. 2021 Feb 23;6(56):eabf6692.
doi: 10.1126/sciimmunol.abf6692.
Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients


Yu Zhao ^{# 1 2 3 4} , Christoph Kilian ^{# 1} , Jan-Eric Turner ^{# 3 5} , Lidia Bosurgi ^{# 6 7} , Kevin Roedl ^{# 8} , Patricia Bartsch ¹ , Ann-Christin Gnirck ^{3 5} , Filippo Cortesi ⁶ , Christoph Schulthei? ⁹ , Malte Hellmig ¹ , Leon U B Enk ¹ , Fabian Hausmann ² , Alina Borchers ¹ , Milagros N Wong ⁵ , Hans-Joachim Paust ¹ , Francesco Siracusa ⁶ , Nicola Scheibel ⁶ , Marissa Herrmann ⁶ , Elisa Rosati ¹⁰ , Petra Bacher ^{10 11} , Dominik Kylies ³ , Dominik Jarczak ⁸ , Marc L?tgehetmann ¹² , Susanne Pfefferle ¹² , Stefan Steurer ¹³ , Julian Schulze Zur-Wiesch ⁶ , Victor G Puelles ⁵ , Jan-Peter Sperhake ¹⁴ , Marylyn M Addo ^{15 16} , Ansgar W Lohse ⁶ , Mascha Binder ⁹ , Samuel Huber ^{3 6} , Tobias B Huber ^{3 5} , Stefan Kluge ⁸ , Stefan Bonn ^{2 3 4} , Ulf Panzer ^{1 3} , Nicola Gagliani ^{17 6 18 19} , Christian F Krebs ^{20 3}



Affiliations

• PMID: 33622974
• DOI: 10.1126/sciimmunol.abf6692

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.