E4BP4 in macrophages induces an anti-inflammatory phenotype that ameliorates the severity of colitis.
Commun Biol
; 7(1): 527, 2024 May 07.
Article
in En
| MEDLINE
| ID: mdl-38714733
ABSTRACT
Macrophages are versatile cells of the innate immune system that work by altering their pro- or anti-inflammatory features. Their dysregulation leads to inflammatory disorders such as inflammatory bowel disease. We show that macrophage-specific upregulation of the clock output gene and transcription factor E4BP4 reduces the severity of colitis in mice. RNA-sequencing and single-cell analyses of macrophages revealed that increased expression of E4BP4 leads to an overall increase in expression of anti-inflammatory genes including Il4ra with a concomitant reduction in pro-inflammatory gene expression. In contrast, knockout of E4BP4 in macrophages leads to increased proinflammatory gene expression and decreased expression of anti-inflammatory genes. ChIP-seq and ATAC-seq analyses further identified Il4ra as a target of E4BP4, which drives anti-inflammatory polarization in macrophages. Together, these results reveal a critical role for E4BP4 in regulating macrophage inflammatory phenotypes and resolving inflammatory bowel diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colitis
/
Macrophages
Limits:
Animals
Language:
En
Journal:
Commun Biol
Year:
2024
Document type:
Article
Affiliation country:
Japón
Country of publication:
Reino Unido