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Updated: Jul 6, 2026

Protocol to Create Chronic Wounds in Diabetic Mice
Published on: September 25, 2019
Depletion of natural killer cells enhances wound healing in diabetic mice
Jacqueline Cavalcante-Silva1,2, Timothy J Koh1,2
1Center for Wound Healing and Tissue Regeneration, University of Illinois at Chicago, Chicago, 60612-7246 Illinois, United States.
Abstract:
Natural killer cells are known for their killing function in infection- and tumor-related responses but also can shape immune responses involved in physiological processes such as wound healing. We recently reported that natural killer cells accumulate in skin wounds and express proinflammatory cytokines that may impede healing. Since impaired wound healing in diabetes is associated with persistent inflammation, the purpose of the present study was to determine whether natural killer cells contribute to impaired skin wound healing in diabetic mice. Here, we show that natural killer cells accumulate at higher levels in wounds in diabetic mice and exhibit less mature phenotypes compared to nondiabetic mice. In addition, local neutralization of CX3CL1 reduced natural killer cell accumulation in wounds of diabetic mice, suggesting that CX3CL1 plays a role in the infiltration of these cells to the wound site. Finally, depletion of natural killer cells in diabetic wounds improved reepithelization and collagen deposition, suggesting that the elevated levels of natural killer cells contribute to impaired healing associated with diabetes.
Insights
Natural killer cells accumulate in diabetic wounds, impairing healing. Depleting these cells improved skin repair in diabetic mice, highlighting their role in diabetes-related wound complications.
Area of Science:
- Immunology
- Wound Healing
- Diabetic Complications
Background:
- Natural killer (NK) cells are immune cells involved in host defense and tissue repair.
- Previous research indicated NK cells in skin wounds may impede healing.
- Diabetes is linked to impaired wound healing and chronic inflammation.
Purpose of the Study:
- To investigate the role of natural killer cells in impaired skin wound healing in diabetic mice.
Main Methods:
- Compared NK cell accumulation and phenotype in diabetic vs. non-diabetic mouse wounds.
- Utilized CX3CL1 neutralization to assess its role in NK cell infiltration.
- Depleted NK cells in diabetic wounds to evaluate healing outcomes.
Main Results:
- Diabetic mouse wounds showed higher NK cell accumulation with less mature phenotypes.
- CX3CL1 neutralization reduced NK cell infiltration in diabetic wounds.
- NK cell depletion significantly improved reepithelialization and collagen deposition in diabetic wounds.
Conclusions:
- Elevated natural killer cell levels contribute to impaired wound healing in diabetes.
- CX3CL1 signaling is implicated in NK cell recruitment to diabetic wounds.
- Targeting NK cells may offer a therapeutic strategy for diabetic wound complications.

