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

Biomedical Reports
T EleftheriadisI Stefanidis

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 com...Continue Reading

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Citations

Jan 14, 2020·Journal of Basic and Clinical Physiology and Pharmacology·Theodoros EleftheriadisIoannis Stefanidis
Jul 21, 2020·BioMed Research International·Hong-Yong SuHua-Feng Liu
Feb 18, 2020·Clinical Rheumatology·Renaud FeltenLaurent Messer
Apr 1, 2020·American Journal of Physiology. Renal Physiology·Su Woong JungJu-Young Moon
Jul 11, 2020·Kidney International·Claudio PonticelliGabriella Moroni

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