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Published on: May 19, 2023
D-dopachrome tautomerase in adipose tissue inflammation and wound repair
Bong-Sung Kim1,2, Pathricia V Tilstam2, Soo Seok Hwang3
1Department of Plastic and Reconstructive Surgery, Hand Surgery - Burn Center, RWTH Aachen University, Aachen, Germany.
Abstract:
D-dopachrome tautomerase (D-DT/MIF-2) is a member of the macrophage migration inhibitory factor (MIF) cytokine superfamily, and a close structural homolog of MIF. MIF and D-DT have been reported to be involved in obesity, but there is little known about the regulation of D-DT in adipose tissue inflammation and wound healing. Subcutaneous adipose tissue was collected from 54 healthy donors and 28 donors with acutely inflamed wounds undergoing wound debridement. In addition, epididymal fat pads of mice were injected with lipopolysaccharide to study receptor expression and cell migration in vivo. D-DT protein levels and mRNA expression were significantly decreased in subcutaneous adipose tissue adjacent to acutely inflamed wounds. D-DT improved fibroblast viability and increased proliferation in vitro. While D-DT alone did not have a significant effect on in vitro fibroblast wound healing, simultaneous addition of neutralizing MIF antibody resulted in a significant improvement of fibroblast wound healing. Interestingly, expression of the MIF and D-DT receptor CD74 was down-regulated while the MIF receptors CXCR2 and CXCR4 were up-regulated primarily on macrophages indicating that the MIF-CXCR2/4 axis may promote recruitment of inflammatory cells into adipose tissue. Our results describe a reciprocal role of D-DT to MIF in inflamed adipose tissue, and indicate that D-DT may be beneficial in wound repair by improving fibroblast survival and proliferation.
Insights
D-dopachrome tautomerase (D-DT) levels decrease in inflamed adipose tissue. D-DT enhances fibroblast survival and proliferation, potentially aiding wound repair, especially when macrophage migration inhibitory factor (MIF) is inhibited.
Area of Science:
- Immunology
- Endocrinology
- Tissue Repair
Background:
- D-dopachrome tautomerase (D-DT) is structurally homologous to macrophage migration inhibitory factor (MIF).
- Both MIF and D-DT are implicated in obesity, but their roles in adipose tissue inflammation and wound healing are unclear.
- Understanding D-DT regulation in adipose tissue is crucial for inflammatory and repair processes.
Purpose of the Study:
- To investigate the regulation and function of D-DT in inflamed adipose tissue and its impact on wound healing.
- To explore the interplay between D-DT, MIF, and their receptors in adipose tissue inflammation.
- To assess D-DT's potential therapeutic role in fibroblast-mediated wound repair.
Main Methods:
- Collected subcutaneous adipose tissue from healthy and inflamed wound donors.
- Utilized mouse models with lipopolysaccharide-injected epididymal fat pads.
- Assessed D-DT protein and mRNA levels, fibroblast viability, proliferation, and wound healing in vitro.
- Analyzed receptor expression (CD74, CXCR2, CXCR4) on macrophages.
Main Results:
- D-DT protein and mRNA expression were significantly reduced in adipose tissue near inflamed wounds.
- D-DT enhanced fibroblast viability and proliferation in vitro.
- D-DT alone did not significantly improve fibroblast wound healing, but MIF antibody co-treatment did.
- MIF receptor CXCR2/4 expression increased on macrophages, suggesting a role in inflammatory cell recruitment.
Conclusions:
- D-DT plays a reciprocal role to MIF in inflamed adipose tissue.
- D-DT may promote wound repair by supporting fibroblast survival and proliferation.
- The MIF-CXCR2/4 axis appears to mediate inflammatory cell recruitment into adipose tissue.
