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Updated: Jun 24, 2026

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The Trim32-DPEP2 axis is an inflammatory switch in macrophages during intestinal inflammation

Zhiyan Zhan1,2, Huisheng Liang3,4, Zhuoqi Zhao5

  • 1Department of Clinical Nutrition, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China. zhanzhiyan@sjtu.edu.cn.

Cell Death and Differentiation
|February 28, 2025
PubMed

Insights

Inflammatory macrophages drive intestinal inflammation. Researchers found Dipeptidase-2 (DPEP2) protein degradation by Trim32 activates inflammatory pathways, suggesting the Trim32-DPEP2 axis as a therapeutic target.

Area of Science:

  • Immunology
  • Gastroenterology
  • Molecular Biology

Background:

  • The precise mechanisms by which inflammatory macrophages contribute to intestinal inflammation remain incompletely understood.
  • Understanding these mechanisms is crucial for developing effective therapeutic strategies for inflammatory bowel diseases.

Purpose of the Study:

  • To elucidate the role of Dipeptidase-2 (DPEP2) in macrophage-mediated intestinal inflammation.
  • To investigate the regulatory axis involving Trim32 and DPEP2 in the context of inflammation.

Main Methods:

  • Integrated analysis of RNA sequencing and mass spectrometry-based quantitative proteomics to compare transcriptomic and proteomic data in activated macrophages.
  • In vivo and in vitro experiments to assess the impact of DPEP2 suppression and degradation on macrophage function and intestinal inflammation.

Main Results:

  • Dipeptidase-2 (DPEP2) protein levels were sharply downregulated in activated macrophages, independent of mRNA levels.
  • Suppression of DPEP2 exacerbated macrophage-mediated intestinal inflammation in vivo and promoted inflammatory pathway activation in vitro.
  • DPEP2 degradation by Trim32 in proinflammatory macrophages led to the activation of NF-κB and p38 MAPK signaling pathways via the release of MAK3K7.

Conclusions:

  • The Trim32-DPEP2 axis plays a critical role in regulating macrophage-mediated intestinal inflammation.
  • DPEP2 acts as a key regulator, with its degradation by Trim32 promoting inflammatory signaling.
  • The Trim32-DPEP2 axis represents a potential therapeutic target for treating intestinal inflammation.

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