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

Published on May 1, 2019in Journal of Investigative Dermatology6.29
· DOI :10.1016/j.jid.2018.10.039
Janaína F. Barros2
Estimated H-index: 2
(UFRJ: Federal University of Rio de Janeiro),
Ingrid Waclawiak1
Estimated H-index: 1
(UFRJ: Federal University of Rio de Janeiro)
+ 10 AuthorsClaudia F. Benjamim23
Estimated H-index: 23
(UFRJ: Federal University of Rio de Janeiro)
Sources
Abstract
Wound healing is 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 wounds are one of the serious long-term complications associated with diabetes mellitus. The chemokine receptor CCR4 and its respective ligands, CCL17 and CCL22, are involved in regulatory T cell recruitment and activation in inflamed skin; however, the role of regulatory T cells in wounds is still not clear. Our aim was to investigate the role of CCR4 and regulatory T cells in cutaneous wound healing in 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 healing and fewer regulatory T cells in 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 CCR4 and regulatory T cells negatively affect wound healing in diabetic mice.
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