Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury

Severe lung damage resulting from COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways, and genes present across the spectrum of histopathological damage in COVID-19-...

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Bibliographic Details
Published in:JCI insight Vol. 8; no. 2
Main Authors: Cross, Amy R., de Andrea, Carlos E., Villalba-Esparza, María, Landecho, Manuel F., Cerundolo, Lucia, Weeratunga, Praveen, Etherington, Rachel E., Denney, Laura, Ogg, Graham, Ho, Ling-Pei, Roberts, Ian S.D., Hester, Joanna, Klenerman, Paul, Melero, Ignacio, Sansom, Stephen N., Issa, Fadi
Format: Journal Article
Language:English
Published: United States American Society for Clinical Investigation 24.01.2023
American Society for Clinical investigation
Subjects:
Antigens
BLyS protein
Cell signaling
Cells
Chemokines
COVID-19
CXCL10 protein
CXCL11 protein
CXCR3 protein
Cytotoxicity
Gene expression
Humans
Hyperplasia
Infections
Inflammation
Lung
Lymphocytes
Macrophages
Pathology
Patients
Pneumonia
Pneumonitis
Proteins
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Stromal cells
Transcriptome
Transcriptomics
COVID-19
Molecular pathology
Inflammation
Cellular immune response
Chemokines
ISSN:2379-3708, 2379-3708
Online Access:Get full text
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Summary:Severe lung damage resulting from COVID-19 involves complex interactions between diverse populations of immune and stromal cells. In this study, we used a spatial transcriptomics approach to delineate the cells, pathways, and genes present across the spectrum of histopathological damage in COVID-19-affected lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from 46 areas of interest covering more than 62,000 cells within well-preserved lung samples from 3 patients. Despite substantial interpatient heterogeneity, we discovered evidence for a common immune-cell signaling circuit in areas of severe tissue that involves crosstalk between cytotoxic lymphocytes and pro-inflammatory macrophages. Expression of IFNG by cytotoxic lymphocytes was associated with induction of chemokines, including CXCL9, CXCL10, and CXCL11, which are known to promote the recruitment of CXCR3+ immune cells. The TNF superfamily members BAFF (TNFSF13B) and TRAIL (TNFSF10) were consistently upregulated in the areas with severe tissue damage. We used published spatial and single-cell SARS-CoV-2 data sets to validate our findings in the lung tissue from additional cohorts of patients with COVID-19. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies.
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Authorship note: SNS and FI are co–senior authors.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.157837