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

Janaína F. Barros, Ingrid Waclawiak, Cyntia Pecli, Paula A. Borges, Janaína L. Georgii, Erivan S. Ramos-Junior, Claudio Canetti, Tristan Courau, David Klatzmann, Steven L. Kunkel, Carmen Penido, Fábio B. Canto, Claudia F. Benjamim

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1161-1170
Number of pages10
JournalJournal of Investigative Dermatology
Issue number5
StatePublished - May 2019
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


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