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 - Funding Information:
We greatly acknowledge the late Ariane Rennó Brogliato for her contribution to the conception, design, analysis, and interpretation of the manuscript, and as mentor to Janaína F. Barros, it was of great significance. This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - Universal 474437/2013-2; PQ1D 311536/2015-8; Diabetes 563899/2010-7) and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ - Cientista do Nosso Estado- CNE E_05/2015 - grant #215274). The scholarship was from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. We thank Julio Scharfstein for generous support with the RT-PCR experiments.
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.
UR - http://www.scopus.com/inward/record.url?scp=85060766154&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060766154&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2018.10.039
DO - 10.1016/j.jid.2018.10.039
M3 - Article
C2 - 30465800
AN - SCOPUS:85060766154
VL - 139
SP - 1161
EP - 1170
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 5
ER -