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

• Published in: Science immunology 2021-02, Vol.6 (56)
• Main 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, 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.
• Format: Article
• Language: English
• ISSN: 2470-9468; 2470-9468
• DOI: 10.1126/sciimmunol.abf6692

Tissue-resident memory-like T H 17 cells are clonally expanded in bronchoalveolar lavage fluid of patients with severe COVID-19. Generation of T helper 17 (T H 17) cells has been associated with immunopathogenesis in multiple autoimmune diseases. Using integrated single-cell transcriptome and TCR repertoire profiling, Zhao et al . showed that a population of T H 17 cells with features of tissue-resident memory T cells was clonally expanded in bronchoalveolar lavage (BAL) fluid collected from the lungs of patients with severe COVID-19, but not in samples from patients with bacterial pneumonia. Lung tissue–resident memory-like T H 17 cells were the primary immune cell type in BAL expressing the cytokine GM-CSF, which was also elevated in serum from a cohort of patients with severe COVID-19 compared with those with moderate disease. These results provide insight into specific T cell responses associated with severe COVID-19 pneumonia and identify a potential cellular target of GM-CSF–neutralizing therapies. 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.