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DPEP2 deficiency enhances infiltration of macrophages by Akt1-VIM axis
Yufen Wu1, Wenxue Liu2, Ying Xiang3
1Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350014, China.
Abstract:
Dipeptidase-2 (DPEP2) is a key regulator of macrophage-mediated intestinal inflammation. DPEP2 deficiency not only enhances the transduction of inflammatory signals in macrophages, but also promotes infiltration of macrophages into colonic tissue. However, the mechanisms via which DPEP2 regulates infiltration of macrophages are not completely understood. Herein, our findings indicate that DPEP2 deletion upregulates the ability of migration and invasion in macrophages. Mechanistically, repressing DPEP2 increased Ser39 phosphorylation of vimentin (VIM), but has no influence on the Ser56 or Ser83 phosphorylation of VIM. DPEP2 impairs Akt1-mediated phosphorylation of VIM by binding VIM. Deleting DPEP2 promotes AKT serine/threonine kinase 1 (Akt1)-mediated activation of VIM, resulting in enhanced infiltration of macrophage. Thus, DPEP2 regulates infiltration of macrophages by Akt1-VIM axis, and targeting DPEP2-Akt1-VIM axis may presents a potential therapeutic strategy for macrophage-mediated intestinal inflammation.
Insights
Dipeptidase-2 (DPEP2) deficiency worsens intestinal inflammation by increasing macrophage migration. Targeting the DPEP2-Akt1-Vimentin pathway offers a potential therapeutic strategy for inflammatory conditions.
Area of Science:
- Immunology
- Cell Biology
- Gastroenterology
Background:
- Dipeptidase-2 (DPEP2) regulates macrophage-mediated intestinal inflammation.
- DPEP2 deficiency enhances inflammatory signaling and macrophage infiltration in the colon.
Purpose of the Study:
- To elucidate the mechanisms by which DPEP2 controls macrophage infiltration into colonic tissue.
- To investigate the role of the Akt1-Vimentin axis in DPEP2-regulated macrophage behavior.
Main Methods:
- Investigated macrophage migration and invasion assays in DPEP2-deficient models.
- Analyzed vimentin (VIM) phosphorylation at specific serine residues (Ser39, Ser56, Ser83).
- Examined the interaction between DPEP2, Akt1, and VIM.
Main Results:
- DPEP2 deletion significantly upregulated macrophage migration and invasion.
- Repressing DPEP2 increased Ser39 phosphorylation of vimentin (VIM).
- DPEP2 normally inhibits Akt1-mediated VIM phosphorylation; its deletion promotes this activation, enhancing macrophage infiltration.
Conclusions:
- DPEP2 regulates macrophage infiltration via the Akt1-Vimentin signaling axis.
- Targeting the DPEP2-Akt1-Vimentin pathway presents a potential therapeutic strategy for intestinal inflammation.
