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

Abstract

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 TH17 cells (TRM17 cells) in the lungs even after viral clearance. These TRM17 cells were characterized by 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 patients with COVID-19 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.