title: Impaired T-cell differentiation in diabetic foot ulceration.
abstract: Foot ulceration is one of the most debilitating complications associated with diabetes, but its cause remains poorly understood. Several studies have been undertaken to understand healing kinetics or find possible therapies to enhance healing. However, few studies have been directed at understanding the immunological alterations that could influence wound healing in diabetes. In this study, we analysed the T-cell receptor (TCR) repertoire diversity in TCR-αβ+T cells. We also analysed the distribution and phenotype of T cells obtained from the peripheral blood of healthy controls and diabetic individuals with or without foot ulcers. Our results showed that diabetic individuals, especially those with foot ulcers, have a significantly lower naive T-cell number and a poorer TCR-Vβ repertoire diversity. We also showed that the reduced TCR-Vβ repertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells, the major source of tumour necrosis factor-α production, which was even more pronounced in patients with acute foot ulceration. Moreover, the expression of several inflammatory chemokine receptors was significantly reduced in diabetic patients. In conclusion, effector T-cell accumulation and TCR repertoire diversity reduction appear to precede the development of foot ulcers. This finding may open new immunological therapeutic possibilities and provide a new prognostic tool in diabetic wound care.
authors.affiliation: Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Moura
authors.affiliation: Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), 4099-001 Porto, Portugal.|Unidade Multidisciplinar de Investigação Biomédica (UMIB/ICBAS/UP), Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Rodrigues
authors.affiliation: Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), 4099-001 Porto, Portugal.|Unidade Multidisciplinar de Investigação Biomédica (UMIB/ICBAS/UP), Porto, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Gonçalves
authors.affiliation: Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), 4099-001 Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Amaral
authors.affiliation: Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), 4099-001 Porto, Portugal.|Unidade Multidisciplinar de Investigação Biomédica (UMIB/ICBAS/UP), Porto, Portugal.|These authors contributed equally to this work.
authors.forename: Margarida
authors.initials: M
authors.lastname: Lima
authors.affiliation: Center for Neuroscience and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, Portugal.|Department of Geriatrics, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72202, USA.|Arkansas Children's Hospital Research Institute (ACHRI), Little Rock, AR 72202, USA.|These authors contributed equally to this work.
authors.forename: Eugénia
authors.initials: E
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D017719:Diabetic Foot / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D056426:Genetic Loci; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000473:pathology*
chemical_list: D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019707:Receptors, Chemokine