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

AI Article Synopsis

  • - The study investigates lung tissue damage from COVID-19, focusing on the interactions between immune and stromal cells using a method called spatial transcriptomics to analyze over 62,000 cells from lung samples of 3 patients.
  • - Researchers identified a common immune signaling circuit in severely damaged areas, highlighting communication between cytotoxic lymphocytes and pro-inflammatory macrophages, along with specific chemokines that attract certain immune cells.
  • - The findings, supported by additional patient data, aim to enhance understanding of immune responses in severe COVID-19 cases and may guide the development of future therapies.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977306PMC
http://dx.doi.org/10.1172/jci.insight.157837DOI Listing

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