Mehta, P., Sanz-Magallón Duque de Estrada, B., Denneny, E.K. et al. (14 more authors) (2024) Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease. Frontiers in Immunology, 15. 1372658. ISSN 1664-3224
Abstract
Background: Persistent radiological lung abnormalities are evident in many survivors of acute coronavirus disease 2019 (COVID-19). Consolidation and ground glass opacities are interpreted to indicate subacute inflammation whereas reticulation is thought to reflect fibrosis. We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis.
Methods: We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern, targeting lung segments affected by the predominant abnormality.
Results: CD4 central memory T cells and CD8 effector memory T cells were significantly more abundant in those with inflammatory radiology. Clustering of similar TCRs from multiple donors was a striking feature of both phenotypes, consistent with tissue localised antigen-specific immune responses. There was no enrichment for known SARS-CoV-2-reactive TCRs, raising the possibility of T cell-mediated immunopathology driven by failure in immune self-tolerance.
Conclusions: Post-COVID radiological inflammation and fibrosis show evidence of shared antigen-specific T cell responses, suggesting a role for therapies targeting T cells in limiting post-COVID lung damage.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 Mehta, Sanz-Magallón Duque de Estrada, Denneny, Foster, Turner, Mayer, Milighetti, Platé, Worlock, Yoshida, Brown, Nikolić, Chain, Noursadeghi, Chambers, Porter and Tomlinson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. http://creativecommons.org/licenses/by/4.0/ |
Keywords: | COVID-19; SARS-CoV-2; T cell receptor; fibrosis; inflammation; scRNAseq; Humans; COVID-19; Single-Cell Analysis; SARS-CoV-2; Male; Female; Middle Aged; Receptors, Antigen, T-Cell; Pulmonary Fibrosis; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Lung; Aged; Adult; Inflammation; Bronchoalveolar Lavage Fluid; Memory T Cells; Transcriptome |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Funding Information: | Funder Grant number Medical Research Council MR/N007727/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 31 Jan 2025 10:49 |
Last Modified: | 31 Jan 2025 10:49 |
Status: | Published |
Publisher: | Frontiers Media SA |
Refereed: | Yes |
Identification Number: | 10.3389/fimmu.2024.1372658 |
Related URLs: | |
Sustainable Development Goals: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222468 |