Soluble CD83-modulated pro-resolving macrophages strongly improve wound healing processes

• Applicant: Dr. Dmytro Royzman
• Subject Area: Dermatology ; Immunology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 579039423

The overall goal of this proposal is to investigate the pro-regenerative capacities of sCD83 in cutaneous wound healing under challenging conditions. In a recent study, we demonstrated that sCD83 significantly accelerates wound healing in healthy C57BL/6 mice. This process involves macrophages undergoing a transdifferentiation from a pro-inflammatory to a pro-resolving phenotype following sCD83 administration. To explore the role of CD83 and sCD83 in wound healing, this proposal focuses on three main objectives: #1: TLR4 is the binding site for sCD83. This objective aims to investigate the in vivo relevance of the TLR4/MD-2-CD83 axis during wound healing and its modulation by sCD83. Using knockout mice for TLR4, MD-2, TRIF, MyD88, and IRF-3, we will compare wound healing processes under systemic sCD83 treatment. This includes histological and molecular analyses of wound tissue. #2: Impaired macrophage activity is associated with delayed wound healing and the formation of chronic wounds. To evaluate the therapeutic potential of sCD83, we will investigate whether sCD83 can restore wound healing in aged and diabetic mice. Wound healing will be analyzed on histological, cellular, and molecular levels. In a second approach, we will repeat these experiments in an ischemia/reperfusion model to mimic the situation in bedridden patients and assess whether sCD83 therapy can mitigate the formation of pressure ulcers. #3: The specific deletion of CD83 in various immune cells, such as DCs, Tregs, and macrophages, results in a pro-inflammatory phenotype and impaired resolution of inflammation in these conditional knockout animals. We will study the role of CD83-expressing macrophages during wound healing by examining the wound healing process in mice with a specific knockout of CD83 in Cx3CR1-expressing cells on histological, cellular, and molecular levels.

• DFG Programme: Research Grants