Scientific publications
- [COMBINATION STRATEGIES FOR TRANSLATIONAL IMMUNOTHERAPY]
- [IMMUNOLOGY AND IMMUNOTHERAPY]
- [CANCER DIVISION]
Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury
Amy R Cross 1, Carlos E de Andrea 2, María Villalba-Esparza 2, Manuel F Landecho 3 4, Lucia Cerundolo 1, Praveen Weeratunga 5, Rachel E Etherington 5, Laura Denney 5, Graham Ogg 5, Ling-Pei Ho 5, Ian Sd Roberts 6, Joanna Hester 1, Paul Klenerman 7, Ignacio Melero 4 8 9, Stephen N Sansom 10, Fadi Issa 1
Abstract
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.
CITA DEL ARTÍCULO JCI Insight. 2023 Jan 24;8(2):e157837. doi: 10.1172/jci.insight.157837.
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