Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury
<p>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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2022
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| _version_ | 1826310539373969408 |
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| author | Cross, AR de Andrea, CE Villalba-Esparza, M Landecho, MF Cerundolo, L Weeratunga, P Etherington, RE Denney, L Ogg, G Ho, L-P Roberts, IS Hester, J Klenerman, P Melero, I Sansom, SN Issa, F |
| author_facet | Cross, AR de Andrea, CE Villalba-Esparza, M Landecho, MF Cerundolo, L Weeratunga, P Etherington, RE Denney, L Ogg, G Ho, L-P Roberts, IS Hester, J Klenerman, P Melero, I Sansom, SN Issa, F |
| author_sort | Cross, AR |
| collection | OXFORD |
| description | <p>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 <em>IFNG</em> by cytotoxic lymphocytes was associated with induction of chemokines, including <em>CXCL9</em>, <em>CXCL10</em>, and <em>CXCL11</em>, which are known to promote the recruitment of CXCR3<sup>+</sup> immune cells. The TNF superfamily members <em>BAFF</em> (<em>TNFSF13B</em>) and <em>TRAIL</em> (<em>TNFSF10</em>) 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.</p> |
| first_indexed | 2024-03-07T07:55:01Z |
| format | Journal article |
| id | oxford-uuid:c1e619c9-0827-42bd-a526-338bf01dffd2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:55:01Z |
| publishDate | 2022 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | oxford-uuid:c1e619c9-0827-42bd-a526-338bf01dffd22023-08-04T12:54:52ZSpatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injuryJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c1e619c9-0827-42bd-a526-338bf01dffd2EnglishSymplectic ElementsAmerican Society for Clinical Investigation2022Cross, ARde Andrea, CEVillalba-Esparza, MLandecho, MFCerundolo, LWeeratunga, PEtherington, REDenney, LOgg, GHo, L-PRoberts, ISHester, JKlenerman, PMelero, ISansom, SNIssa, F<p>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 <em>IFNG</em> by cytotoxic lymphocytes was associated with induction of chemokines, including <em>CXCL9</em>, <em>CXCL10</em>, and <em>CXCL11</em>, which are known to promote the recruitment of CXCR3<sup>+</sup> immune cells. The TNF superfamily members <em>BAFF</em> (<em>TNFSF13B</em>) and <em>TRAIL</em> (<em>TNFSF10</em>) 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.</p> |
| spellingShingle | Cross, AR de Andrea, CE Villalba-Esparza, M Landecho, MF Cerundolo, L Weeratunga, P Etherington, RE Denney, L Ogg, G Ho, L-P Roberts, IS Hester, J Klenerman, P Melero, I Sansom, SN Issa, F Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury |
| title | Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury |
| title_full | Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury |
| title_fullStr | Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury |
| title_full_unstemmed | Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury |
| title_short | Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury |
| title_sort | spatial transcriptomic characterization of covid 19 pneumonitis identifies immune circuits related to tissue injury |
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