IFN‐γ enhances the wound healing effect of late EPCs (LEPCs) via BST2‐mediated adhesion to endothelial cells

Abstract

Circulating late endothelial progenitor cells (LEPCs) home to injured vessels, initiating blood vessel regeneration. This process requires the initial adhesion of LEPCs to endothelial cells within the wounded site. In this study, treating LEPCs with IFN-γ enhanced wound healing through BST2-mediated adhesion to endothelial cells. We found that IFN-γ significantly upregulated BST2 expression in both LEPCs and ECs and increased tube formation in LEPCs. Upregulated BST2 increased LEPC adhesion to ECs through a tight homophilic interaction of its extracellular domain. Finally, when the IFN-γ-treated LEPCs were injected into the wounded mouse tail vein, superior therapeutic effects of wound closure were observed. This study provides a useful application to enhance the adhesion of LEPCs for vessel regeneration and wound closure.

Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation

“…Regarding the role of IFN-γ in skin wounds, we previously reported that IFN-γ plays a key role in the early phase of the wound healing process in a study on mice deficient in invariant natural killer T ( i NKT) cells, which are major IFN-γ-producing cells [21]. In addition, IFN-γ-treated LEPCs, which initiate blood vessel regeneration [22], or TNF-α- and IFN-γ-treated monocytes/macrophages [18] have been reported to be involved in the promotion of wound healing. In the current study, IFN-γKO mice exhibited significant attenuation in wound closure on Day 10 in association with prolonged neutrophil accumulation.…”

The immunologic changes during different phases of intestinal anastomotic healing

“…Its effects on cells are remarkable and have been found to regulate the expression of thousands human genes. Although IFN‐γhas functions of anti viral, it is more notable for stimulating and regulating the immune cells 92,93 …”

“…IFN‐γ is basically secreted by CD4 + and NK cells, and it contributes mainly to the activation of immune cells and has relationships with both neutrophil recruitment and cell clearance 95,96 . As for its role in wound healing, some studies show that it can enhance the healing procedure and effects, such as IFN‐γ enhances the blood vascular regeneration and wound healing through significantly upregulated BST2 expression in both LEPCs and ECs and increased tube formation in LEPCs 92 …”