TY - JOUR
T1 - Role of Chemokine Receptor CCR4 and Regulatory T Cells in Wound Healing of Diabetic Mice
AU - Barros, Janaína F.
AU - Waclawiak, Ingrid
AU - Pecli, Cyntia
AU - Borges, Paula A.
AU - Georgii, Janaína L.
AU - Ramos-Junior, Erivan S.
AU - Canetti, Claudio
AU - Courau, Tristan
AU - Klatzmann, David
AU - Kunkel, Steven L.
AU - Penido, Carmen
AU - Canto, Fábio B.
AU - Benjamim, Claudia F.
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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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U2 - 10.1016/j.jid.2018.10.039
DO - 10.1016/j.jid.2018.10.039
M3 - Article
C2 - 30465800
AN - SCOPUS:85060766154
SN - 0022-202X
VL - 139
SP - 1161
EP - 1170
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -