Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 02 2023
11 02 2023
Historique:
received:
10
03
2022
accepted:
23
01
2023
entrez:
11
2
2023
pubmed:
12
2
2023
medline:
15
2
2023
Statut:
epublish
Résumé
Prolonged lung pathology has been associated with COVID-19, yet the cellular and molecular mechanisms behind this chronic inflammatory disease are poorly understood. In this study, we combine advanced imaging and spatial transcriptomics to shed light on the local immune response in severe COVID-19. We show that activated adventitial niches are crucial microenvironments contributing to the orchestration of prolonged lung immunopathology. Up-regulation of the chemokines CCL21 and CCL18 associates to endothelial-to-mesenchymal transition and tissue fibrosis within these niches. CCL21 over-expression additionally links to the local accumulation of T cells expressing the cognate receptor CCR7. These T cells are imprinted with an exhausted phenotype and form lymphoid aggregates that can organize in ectopic lymphoid structures. Our work proposes immune-stromal interaction mechanisms promoting a self-sustained and non-resolving local immune response that extends beyond active viral infection and perpetuates tissue remodeling.
Identifiants
pubmed: 36774347
doi: 10.1038/s41467-023-36333-2
pii: 10.1038/s41467-023-36333-2
pmc: PMC9922044
doi:
Substances chimiques
CCL18 protein, human
0
CCL21 protein, human
0
Chemokine CCL21
0
Chemokines, CC
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
791Informations de copyright
© 2023. The Author(s).
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