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    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. © 2024. The Author(s).

    Citation

    Yasuko Kajimura, Akihiko Taguchi, Yuko Nagao, Kaoru Yamamoto, Konosuke Masuda, Kensuke Shibata, Yoichi Asaoka, Makoto Furutani-Seiki, Yukio Tanizawa, Yasuharu Ohta. E4BP4 in macrophages induces an anti-inflammatory phenotype that ameliorates the severity of colitis. Communications biology. 2024 May 07;7(1):527

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    PMID: 38714733

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