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Impaired T-cell differentiation in diabetic foot ulceration

Cellular & Molecular Immunology volume 14, pages 758–769 (2017)Cite this article

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.

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Acknowledgements

This work was financed by FEDER funds by the operational program Factors of Competitivity – COMPETE, by the Portuguese Foundation for Science and Technology (FCT) - EXCL/DTP-PIC/0069/2012, PEst-C/SAU/LA0001/2013 and UID/NEU/04539/2013, the EFSD European Research Programme in Microvascular Complications of Diabetes supported by Novartis, and Forum Hematológico do Norte, Portugal. Eugénia 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.

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Authors and Affiliations

  1. Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, 3004-517, Portugal

    João Moura & Eugénia Carvalho

  2. Hospital de Santo António (HSA), Centro Hospitalar do Porto (CHP), Porto, 4099-001, Portugal

    João Rodrigues, Marta Gonçalves, Cláudia Amaral & Margarida Lima

  3. Unidade Multidisciplinar de Investigação Biomédica (UMIB/ICBAS/UP), Porto, Portugal

    João Rodrigues, Marta Gonçalves & Margarida Lima

  4. Department of Geriatrics, University of Arkansas for Medical Sciences (UAMS), Little Rock, 72202, AR, USA

    Eugénia Carvalho

  5. Arkansas Children's Hospital Research Institute (ACHRI), Little Rock, 72202, AR, USA

    Eugénia Carvalho

  6. These authors contributed equally to this work.,

    Margarida Lima & Eugénia Carvalho

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  1. João Moura
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Correspondence to João Moura.

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Moura, J., Rodrigues, J., Gonçalves, M. et al. Impaired T-cell differentiation in diabetic foot ulceration. Cell Mol Immunol 14, 758–769 (2017). https://doi.org/10.1038/cmi.2015.116

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