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dc.creatorCross, A.R. (Amy R.)-
dc.creatorAndrea, C.E. (Carlos Eduardo) de-
dc.creatorVillalba-Esparza, M. (María)-
dc.creatorLandecho, M.F. (Manuel F.)-
dc.creatorCerundolo, L. (Lucia)-
dc.creatorWeeratunga, P. (Praveen)-
dc.creatorEtherington, R.E. (Rachel E.)-
dc.creatorDenney, L. (Laura)-
dc.creatorOgg, G. (Graham)-
dc.creatorHo, L.P. (Ling-Pei)-
dc.creatorRoberts, I.S.D. (Ian S. D.)-
dc.creatorHester, J. (Joanna)-
dc.creatorKlenerman, P. (Paul)-
dc.creatorMelero, I. (Ignacio)-
dc.creatorSansom, S.N. (Stephen N.)-
dc.creatorIssa, F. (Fadi)-
dc.date.accessioned2023-04-18T08:45:07Z-
dc.date.available2023-04-18T08:45:07Z-
dc.date.issued2023-
dc.identifier.citationCross, A. R.; De Andrea, C. (Carlos Eduardo); Villalba-Esparza, M. (María); et al. "Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury". JCI Insight. 8 (2), 2023, e157837es
dc.identifier.issn2379-3708-
dc.identifier.urihttps://hdl.handle.net/10171/65968-
dc.description.abstractSevere 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.-
dc.language.isoen-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.titleSpatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury-
dc.typeinfo:eu-repo/semantics/article-
dc.description.noteThis is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.-
dc.identifier.doi10.1172/jci.insight.157837-
dadun.citation.number2-
dadun.citation.publicationNameJCI Insight-
dadun.citation.startingPagee157837-
dadun.citation.volume8-
dc.identifier.pmid36472908-

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