DPEP2 deficiency enhances infiltration of macrophages by Akt1-VIM axis.

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.