Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization

Fang-Ling Zhang, Zhen Hu, Yi-Fan Wang, Wen-Juan Zhang, Bo-Wei Zhou, Qi-Shun Sun, Ze-Bin Lin and Ke-Xuan Liu ()
Additional contact information
Fang-Ling Zhang: Southern Medical University
Zhen Hu: Southern Medical University
Yi-Fan Wang: Southern Medical University
Wen-Juan Zhang: Southern Medical University
Bo-Wei Zhou: Southern Medical University
Qi-Shun Sun: Southern Medical University
Ze-Bin Lin: Southern Medical University
Ke-Xuan Liu: Southern Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-42502-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42502-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-42502-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().