Distinct tissue niches direct lung immunopathology via CCL18 and CCL21 in severe COVID-19.
Nat Commun
; 14(1): 791, 2023 02 11.
Article
in English
| MEDLINE | ID: covidwho-2243508
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Chemokines, CC
/
Chemokine CCL21
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2023
Document Type:
Article
Affiliation country:
S41467-023-36333-2
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