Role of Chemokine Receptor CCR4 and Regulatory T Cells in Wound Healing of Diabetic Mice

Wound healingis a well-coordinated process that involves inflammatory mediators and cellular responses; however, if any disturbances are present during this process, tissue repair is impaired. Chronic woundsare one of the serious long-term complications associated with diabetes mellitus. The chemokine receptor CCR4and its respective ligands, CCL17and CCL22, are involved in regulatory T cellrecruitment and activation in inflamed skin; however, the role of regulatory T cellsin wounds is still not clear. Our aim was to investigate the role of CCR4and regulatory T cellsin cutaneous wound healingin diabetic mice. Alloxan-induced diabetic wild- type mice (diabetic) developed wounds that were difficult to heal, differently from CCR4–/– diabetic mice ( CCR4–/– diabetic), and also from anti- CCL17/22 or anti-CD25–injected diabetic mice that presented with accelerated wound healingand fewer regulatory T cellsin the wound bed. Consequently, CCR4–/– diabetic mice also presented with alteration on T cells population in the wound and draining lymph nodes; on day 14, these mice also displayed an increase of collagen fiber deposition. Still, cytokine levels were decreased in the wounds of CCR4–/– diabetic mice on day 2. Our data suggest that the receptor CCR4and regulatory T cellsnegatively affect wound healingin diabetic mice.