Urate crystals activate directly T-cell receptor complex and induce T-cell proliferation

  • Authors:
    • Theodoros Eleftheriadis
    • Georgios Pissas
    • Maria Sounidaki
    • Georgia Antoniadi
    • Ioannis Tsialtas
    • Vassilios Liakopoulos
    • Ioannis Stefanidis
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  • Published online on: August 4, 2017     https://doi.org/10.3892/br.2017.960
  • Pages: 365-369
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Abstract

Uric acid is a known danger associated molecular pattern molecule able to induce inflammation following internalization of its crystals by cells of the innate immune system. By activating antigen-presenting cells, urate boosts adaptive immunity as well. Furthermore, urate crystals can induce proliferation of isolated T-cells, which are unable to phagocytose crystal particles. In light of the evidence that urate crystals can also activate dendritic cells and macrophages without prior internalization but through sequestration of lipid rafts (and consequently receptors clustering in a non specific manner), the authors evaluated whether such a mechanism is involved in the direct activation of T-cells by urate crystals. In the present study, isolated human T-cells were cultured with or without urate at a concentration above its crystallization level. The expression and phosphorylation state of the T-cell receptor (TCR) complex zeta chain and the expression of the master regulator of cell proliferation c-Myc were assessed by western blotting. T-cell proliferation was measured by bromodeoxyuridine assay. Collectively, the results indicated that urate increased zeta chain phosphorylation indicating that it induces activation of TCR complex directly, since zeta chain phosphorylation takes place at the cell membrane and is a very proximal event in TCR complex-mediated signal transduction. In parallel, urate increased the expression of the transcription factor c-Myc and induced T-cell proliferation. In conclusion, urate crystals directly activate the TCR complex and induce T-cell proliferation.
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October-2017
Volume 7 Issue 4

Print ISSN: 2049-9434
Online ISSN:2049-9442

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Spandidos Publications style
Eleftheriadis T, Pissas G, Sounidaki M, Antoniadi G, Tsialtas I, Liakopoulos V and Stefanidis I: Urate crystals activate directly T-cell receptor complex and induce T-cell proliferation. Biomed Rep 7: 365-369, 2017
APA
Eleftheriadis, T., Pissas, G., Sounidaki, M., Antoniadi, G., Tsialtas, I., Liakopoulos, V., & Stefanidis, I. (2017). Urate crystals activate directly T-cell receptor complex and induce T-cell proliferation. Biomedical Reports, 7, 365-369. https://doi.org/10.3892/br.2017.960
MLA
Eleftheriadis, T., Pissas, G., Sounidaki, M., Antoniadi, G., Tsialtas, I., Liakopoulos, V., Stefanidis, I."Urate crystals activate directly T-cell receptor complex and induce T-cell proliferation". Biomedical Reports 7.4 (2017): 365-369.
Chicago
Eleftheriadis, T., Pissas, G., Sounidaki, M., Antoniadi, G., Tsialtas, I., Liakopoulos, V., Stefanidis, I."Urate crystals activate directly T-cell receptor complex and induce T-cell proliferation". Biomedical Reports 7, no. 4 (2017): 365-369. https://doi.org/10.3892/br.2017.960