Hester, J. (Joanna)
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- Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury(2023) Landecho, M.F. (Manuel F.); Weeratunga, P. (Praveen); Klenerman, P. (Paul); Issa, F. (Fadi); Etherington, R.E. (Rachel E.); Denney, L. (Laura); Roberts, I.S.D. (Ian S. D.); Hester, J. (Joanna); Villalba-Esparza, M. (María); Sansom, S.N. (Stephen N.); Melero, I. (Ignacio); Cerundolo, L. (Lucia); Ogg, G. (Graham); Cross, A.R. (Amy R.); Ho, L.P. (Ling-Pei); Andrea, C.E. (Carlos Eduardo) deSevere 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.