IL-27 accelerates diabetic wound healing by modulating macrophage polarization

Area of Science:

• Immunology
• Wound Healing
• Diabetes Complications

Background:

• Diabetic foot ulcers (DFU) are severe diabetes complications leading to amputation and reduced lifespan.
• The role of Interleukin-27 (IL-27) in diabetic wound healing and its impact on macrophage polarization remain unclear.

Purpose of the Study:

• To investigate IL-27 expression in diabetic skin.
• To determine if IL-27 supplementation can promote diabetic wound healing by modulating macrophage polarization.

Main Methods:

• Established streptozotocin (STZ)-induced diabetic mouse models with diabetic wounds.
• Assessed protein expression via Western Blotting (WB) and Immunohistochemistry (IHC).
• Utilized macrophage cell lines (RAW264.7) and primary bone marrow-derived macrophages (BMDMs) treated with IL-27 under high glucose (HG) conditions, and employed IL-27 receptor knockout mice.

Main Results:

• IL-27 expression was significantly decreased in diabetic mouse skin.
• IL-27 supplementation promoted diabetic wound healing in vivo.
• In vitro, IL-27 alleviated HG-induced suppression of macrophage functions (iNOS, IL-1β expression, migration, phagocytosis).
• IL-27 promoted M1-to-M2 macrophage polarization via the IL-27-IL-27Rα-p-STAT3 pathway, enhancing diabetic wound healing.

Conclusions:

• Decreased IL-27 expression and impaired STAT3 activation in diabetic skin hinder M1 macrophage polarization, delaying wound healing.
• IL-27 supplementation promotes M1-to-M2 macrophage polarization and accelerates diabetic wound healing.
• IL-27 represents a promising therapeutic target for diabetic foot ulcers (DFU).