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ROLE OF CHEMOKINE RECEPTOR CCR4 AND REGULATORY T CELLS IN WOUND HEALING OF DIABETIC MICE
Barros, Janaína F. et al. | Date Issued: 2019
Author
Barros, Janaína F.
Waclawiak, Ingrid
Pecli, Cyntia
Borges, Paula A.
Georgii, Janaína L.
Ramos-Junior, Erivan S.
Canetti, Claudio
Courau, Tristan
Klatzmann, David
Kunkel, Steven L.
Penido, Carmen
Canto, Fábio B.
Benjamim, Claudia F.
Affilliation
Institute of Biomedical Sciences, Pharmacology and Inflammation Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil
Institute of Biophysics Carlos Chagas Filho, Immunobiology Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil
Institute of Biomedical Sciences, Pharmacology and Inflammation Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil
Institute of Biomedical Sciences, Pharmacology and Inflammation Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil
Institute of Biomedical Sciences, Pharmacology and Inflammation Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil
Institute of Biophysics Carlos Chagas Filho, Immunobiology Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil
Institute of Biophysics Carlos Chagas Filho, Immunobiology Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil
Sorbonne Universités, University of Pierre and Madam Curie, University of Paris, Paris, France
Sorbonne Universités, University of Pierre and Madam Curie, University of Paris, Paris, France / Institut National de la Santé et de la Recherche Médicale les Unités Mixtes de Recherche S959, Paris, France
Department of Pathology, University of Michigan, Ann Arbor, United States
Center for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil / Laboratory of Applied Pharmacology, Institute of Drug Technology, Farmanguinhos, Rio de Janeiro, Brazil
Institute of Microbiology Paulo de Góes, Immunology Department, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil / Department of Immunobiology, Institute of Biology, Fluminense Federal University, Niterói, Brazil
Institute of Biomedical Sciences, Pharmacology and Inflammation Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil / Institute of Biophysics Carlos Chagas Filho, Immunobiology Program, Federal University of Rio de Janeiro, Center for Health Sciences, Rio de Janeiro, Brazil
Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Instituto Nacional de Ciência e Tecnologia de Inovação em Doenças de Populações Negligenciadas. Rio de Janeiro, RJ, Brasil.
Abstract in Portuguese
A cicatrização de feridas é um processo bem coordenado que envolve mediadores inflamatórios e respostas celulares; no entanto, se houver alguma perturbação durante esse processo, o reparo do tecido é prejudicado. Feridas crônicas são uma das complicações graves de longo prazo associadas ao diabetes mellitus. O receptor de quimiocina CCR4 e seus respectivos ligantes, CCL17 e CCL22, estão envolvidos no recrutamento e ativação de células T reguladoras na pele inflamada; no entanto, o papel das células T reguladoras em feridas ainda não está claro. Nosso objetivo foi investigar o papel do CCR4 e das células T reguladoras na cicatrização de feridas cutâneas em camundongos diabéticos. Camundongos selvagens diabéticos induzidos por aloxana (diabéticos) desenvolveram feridas difíceis de cicatrizar, diferentemente de camundongos diabéticos CCR4-/- (CCR4-/- diabéticos) e também de camundongos diabéticos injetados com anti-CCL17/22 ou anti-CD25 que apresentaram cicatrização acelerada de feridas e menos células T reguladoras no leito da ferida. Consequentemente, camundongos diabéticos CCR4-/- também apresentaram alteração na população de células T na ferida e nos linfonodos de drenagem; no dia 14, esses camundongos também apresentaram aumento na deposição de fibras de colágeno. Ainda assim, os níveis de citocina foram diminuídos nas feridas de camundongos diabéticos CCR4-/- no dia 2. Nossos dados sugerem que o receptor CCR4 e as células T reguladoras afetam negativamente a cicatrização de feridas em camundongos diabéticos.
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.
Keywords in Portuguese
macrófago
alvos
memória
reparo
 
Keywords
macrophage
targets
repair
memory
 
Publisher
Elsevier B.V.
Citation
BARROS, Janaína F.; WACLAWIAK, Ingrid; PECLI, Cyntia; BORGES, Paula A.; GEORGII, Janaína L.; RAMOS-JUNIOR, Erivan S.; CANETTI, Claudio; COURAU, Tristan; KLATZMANN, David; KLATZMANN, David; KUNKEL, Steven L.; PENIDO, Carmen; PENIDO, Carmen; CANTO, Fábio B.; CANTO, Fábio B.; BENJAMIM, Claudia F.; BENJAMIM, Claudia F. Role of Chemokine Receptor CCR4 and Regulatory T Cells in Wound Healing of Diabetic Mice. Journal of Investigative Dermatology, United States, v. 139, n. 5, p. 1161-1161, 2019. DOI: 10.1016/J.JID.2018.10.039.
DOI
10.1016/J.JID.2018.10.039
ISSN
0022-202X