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 thera...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-Vβrepertoire diversity.We also showed that the reduced TCR-Vβrepertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells,the major source of tumour necrosis factor-αproduction,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.展开更多
Diabetes is a growing epidemic due to the systematic increase in overweight and obesity,and chronic diabetic foot ulcers(DFUs)are the most debilitating and costly complication of diabetes.Prevention is still essential...Diabetes is a growing epidemic due to the systematic increase in overweight and obesity,and chronic diabetic foot ulcers(DFUs)are the most debilitating and costly complication of diabetes.Prevention is still essential for DFU care,but early detection is limited because we do not have a good DFU biomarker.Here,we report the preliminary results of a large longitudinal study to test the effectiveness of the use of T-cell phenotype and TCR repertoire diversity as DFU biomarkers.Our results show that the ratio of effector/naïve T-cells and the number of TCR expansions are valuable biomarkers of DFU prognosis.展开更多
基金financed by FEDER funds by the operational program Factors of Competitivity–COMPETEthe Portuguese Foundation for Science and Technology(FCT)-EXCL/DTP-PIC/0069/2012,PEst-C/SAU/LA0001/2013 and UID/NEU/04539/2013+1 种基金the EFSD European Research Programme in Microvascular Complications of Diabetes supported by Novartis,and Forum Hematológico do Norte,PortugalEugénia Carvalho is partly funded by the Arkansas Biosciences Institute,the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000,NIH P30AG028718,and NIH RO1 AG033761.
文摘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-Vβrepertoire diversity.We also showed that the reduced TCR-Vβrepertoire diversity in diabetic individuals was mainly owing to the accumulation of effector T cells,the major source of tumour necrosis factor-αproduction,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.
基金We acknowledge support from the Sociedade Portuguesa de Diabetologia(SPD):Bolsa Almeida Ruas 2016,FEDER-strategic project COMPETE:POCI-01-0145-FEDER-007440,European Foundation for the Study of Diabetes(EFSD)and HealthyA-ging2020:CENTRO-01-0145-FEDER-000012N2323
文摘Diabetes is a growing epidemic due to the systematic increase in overweight and obesity,and chronic diabetic foot ulcers(DFUs)are the most debilitating and costly complication of diabetes.Prevention is still essential for DFU care,but early detection is limited because we do not have a good DFU biomarker.Here,we report the preliminary results of a large longitudinal study to test the effectiveness of the use of T-cell phenotype and TCR repertoire diversity as DFU biomarkers.Our results show that the ratio of effector/naïve T-cells and the number of TCR expansions are valuable biomarkers of DFU prognosis.
