A correctable immune niche for epithelial stem-cell reprogramming and post-viral lung diseases.
J Clin Invest
; 2024 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-39052353
ABSTRACT
Epithelial barriers are programmed for defense and repair but are also the site of long-term structural remodeling and disease. In general, this paradigm features epithelial stem cell (ESCs) that are called on to regenerate damaged tissues but can also be reprogrammed for detrimental remodeling. Here we identified a Wfdc21-dependent monocyte-derived dendritic cell (moDC) population that functioned as an early sentinel niche for basal-ESC reprogramming in mouse models of epithelial injury after respiratory viral infection. Niche function depended on moDC delivery of ligand GPNMB to basal-ESC receptor CD44 so that properly timed antibody blockade of ligand or receptor provided long-lasting correction of reprogramming and broad disease phenotypes. These same control points worked directly in mouse and human basal-ESC organoids. Together, the findings identify a mechanism to explain and modify what is otherwise a stereotyped but sometimes detrimental response to epithelial injury.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article