학술논문
Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection.
Document Type
Article
Author
Yang, Chen Xi; Tomchaney, Michael; Landecho, Manuel F.; Zamacona, Borja R.; Marin Oto, Marta; Zulueta, Javier; Malo, Joshua; Knoper, Steve; Contoli, Marco; Papi, Alberto; Vasilescu, Dragoş M.; Sauler, Maor; Straub, Christof; Tan, Cheryl; Martinez, Fernando D.; Bhattacharya, Deepta; Rosas, Ivan O.; Kheradmand, Farrah; Hackett, Tillie-Louise; Polverino, Francesca
Source
Subject
*CHRONIC obstructive pulmonary disease
*SARS-CoV-2
*OBSTRUCTIVE lung diseases
*T cell differentiation
*LUNGS
*T cell receptors
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Language
ISSN
2073-4409
Abstract
People with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling. The parenchyma, airways, and vessels of COPD patients, compared to control lungs had (1) significant enrichment for lung-resident CD45RO+ memory CD4+ T cells; (2) downregulation of genes associated with T cell antigen priming and memory T cell differentiation; and (3) higher expression of proteins associated with SARS-CoV-2 entry and primary receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. In conclusion, the lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory CD4 T cell response and a more invasive SARS-CoV-2 infection pattern and may underlie the higher death toll observed with COVID-19. [ABSTRACT FROM AUTHOR]