Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury
Severe lung damage in 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 lung tissue....
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Sprog: | English |
| Udgivet: |
American Society for Clinical Investigation
2023
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| _version_ | 1826311178085728256 |
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| author | Cross, AR de Andrea, CE María, V-E Landecho Acha, MF Cerundolo, L Weeratunga, P Etherington, R Denney, L Ogg, G Ogg, G Ho, LP Roberts, ISD Hester, J Klenerman, P Melero, I Sansom, SN Issa, F |
| author_facet | Cross, AR de Andrea, CE María, V-E Landecho Acha, MF Cerundolo, L Weeratunga, P Etherington, R Denney, L Ogg, G Ogg, G Ho, LP Roberts, ISD Hester, J Klenerman, P Melero, I Sansom, SN Issa, F |
| author_sort | Cross, AR |
| collection | OXFORD |
| description | Severe lung damage in 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 lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from areas of interest within well preserved post-mortem lung samples from three patients. Despite substantial inter-patient 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 tumour necrosis factor (TNF) superfamily members BAFF ( TNFSF13B ) and TRAIL ( TNFSF10 ) were found to be consistently upregulated in the areas with severe tissue damage. We used published spatial and single cell SARS-CoV-2 datasets to confirm our findings in the lung tissue from additional cohorts of COVID-19 patients. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies. <h4>One Sentence Summary</h4> Spatial analysis identifies IFNγ response signatures as focal to severe alveolar damage in COVID-19 pneumonitis. |
| first_indexed | 2024-03-07T08:04:30Z |
| format | Journal article |
| id | oxford-uuid:05918bdf-af8f-42b6-9f71-3aca57a1f471 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:04:30Z |
| publishDate | 2023 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | oxford-uuid:05918bdf-af8f-42b6-9f71-3aca57a1f4712023-10-24T08:08:57ZSpatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injuryJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:05918bdf-af8f-42b6-9f71-3aca57a1f471EnglishSymplectic ElementsAmerican Society for Clinical Investigation2023Cross, ARde Andrea, CEMaría, V-ELandecho Acha, MFCerundolo, LWeeratunga, PEtherington, RDenney, LOgg, GOgg, GHo, LPRoberts, ISDHester, JKlenerman, PMelero, ISansom, SNIssa, FSevere lung damage in 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 lung tissue. We applied correlation network-based approaches to deconvolve gene expression data from areas of interest within well preserved post-mortem lung samples from three patients. Despite substantial inter-patient 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 tumour necrosis factor (TNF) superfamily members BAFF ( TNFSF13B ) and TRAIL ( TNFSF10 ) were found to be consistently upregulated in the areas with severe tissue damage. We used published spatial and single cell SARS-CoV-2 datasets to confirm our findings in the lung tissue from additional cohorts of COVID-19 patients. The resulting model of severe COVID-19 immune-mediated tissue pathology may inform future therapeutic strategies. <h4>One Sentence Summary</h4> Spatial analysis identifies IFNγ response signatures as focal to severe alveolar damage in COVID-19 pneumonitis. |
| spellingShingle | Cross, AR de Andrea, CE María, V-E Landecho Acha, MF Cerundolo, L Weeratunga, P Etherington, R Denney, L Ogg, G Ogg, G Ho, LP Roberts, ISD 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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