Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation
Abstract: Efficient clearance of dying cells (efferocytosis) is an evolutionarily conserved process for tissue homeostasis. Genetic enhancement of efferocytosis exhibits therapeutic potential for inflammation resolution and tissue repair. However, pharmacological approaches to enhance efferocytosis remain sparse due to a lack of targets for modulation. Here, we report the identification of columbamine (COL) which enhances macrophage‐mediated efferocytosis and attenuates intestinal inflammation in a murine colitis model. COL enhances efferocytosis by promoting LC3‐associated phagocytosis (LAP), a non‐canonical form of autophagy. Transcriptome analysis and pharmacological characterization revealed that COL is a biased agonist that occupies a part of the ligand binding pocket of formyl peptide receptor 2 (FPR2), a G‐protein coupled receptor involved in inflammation regulation. Genetic ablation of the Fpr2 gene or treatment with an FPR2 antagonist abolishes COL‐induced efferocytosis, anti‐colitis activity and LAP. Taken together, our study identifies FPR2 as a potential target for modulating LC3‐associated efferocytosis to alleviate intestinal inflammation and highlights the therapeutic value of COL, a natural and biased agonist of FPR2, in the treatment of inflammatory bowel disease.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation ; day:22 ; month:11 ; year:2023 ; extent:22
EMBO molecular medicine / European Molecular Biology Organization ; (22.11.2023) (gesamt 22)
- Urheber
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Wu, Ming‐Yue
Ge, Yun‐Jun
Wang, Er‐Jin
Liao, Qi‐Wen
Ren, Zheng‐Yu
Yu, Yang
Zhu, Guoyuan
Liu, Chun‐Ping
Zhang, Meng‐Ni
Su, Huanxing
Shen, Han‐Ming
Chen, Ye
Wang, Lei
Wang, Yi‐Tao
Li, Min
Bian, Zhaoxiang
Chai, Jin
Ye, Richard D.
Lu, Jia‐Hong
- DOI
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10.15252/emmm.202317815
- URN
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urn:nbn:de:101:1-2023112314383350602976
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:36 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Wu, Ming‐Yue
- Ge, Yun‐Jun
- Wang, Er‐Jin
- Liao, Qi‐Wen
- Ren, Zheng‐Yu
- Yu, Yang
- Zhu, Guoyuan
- Liu, Chun‐Ping
- Zhang, Meng‐Ni
- Su, Huanxing
- Shen, Han‐Ming
- Chen, Ye
- Wang, Lei
- Wang, Yi‐Tao
- Li, Min
- Bian, Zhaoxiang
- Chai, Jin
- Ye, Richard D.
- Lu, Jia‐Hong
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