Ryan Webb1, Matlock Jeffries, Amr H Sawalha. 1. Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Abstract
BACKGROUND: Abnormally high serum uric acid levels have been associated with several disease conditions including gout and kidney stone disease. More recently, it was shown that uric acid crystals stimulate dendritic cell maturation, activate the NALP3 inflammasome, and enhance antigen-specific immune responses. We hypothesize that uric acid can also stimulate T cells directly and in the absence of antigen presentation. METHODS: Purified primary human T cells were incubated with and without uric acid at concentrations of 50, 100, 150, and 200 microg/mL. The expression of T-cell activation markers CD25 and CD70 was assessed by flow cytometry. In other experiments, Jurkat T cells were used and the expression of the costimulatory molecule CD70 was determined at the mRNA level. RESULTS: Uric acid directly activates primary human T cells in the absence of antigen presentation. Furthermore, primary human T cells and Jurkat T cells treated with uric acid overexpress the costimulatory molecule CD70, which plays an important role in T cell-B cell interaction and antibody production. CONCLUSIONS: The finding that uric acid directly promotes T-cell activation in an antigen-independent system is novel and might play a mechanistic role in the inflammatory response observed in gouty arthritis and other immune-mediated diseases.
BACKGROUND: Abnormally high serum uric acid levels have been associated with several disease conditions including gout and kidney stone disease. More recently, it was shown that uric acid crystals stimulate dendritic cell maturation, activate the NALP3 inflammasome, and enhance antigen-specific immune responses. We hypothesize that uric acid can also stimulate T cells directly and in the absence of antigen presentation. METHODS: Purified primary human T cells were incubated with and without uric acid at concentrations of 50, 100, 150, and 200 microg/mL. The expression of T-cell activation markers CD25 and CD70 was assessed by flow cytometry. In other experiments, Jurkat T cells were used and the expression of the costimulatory molecule CD70 was determined at the mRNA level. RESULTS:Uric acid directly activates primary human T cells in the absence of antigen presentation. Furthermore, primary human T cells and Jurkat T cells treated with uric acid overexpress the costimulatory molecule CD70, which plays an important role in T cell-B cell interaction and antibody production. CONCLUSIONS: The finding that uric acid directly promotes T-cell activation in an antigen-independent system is novel and might play a mechanistic role in the inflammatory response observed in gouty arthritis and other immune-mediated diseases.
Authors: M J Gold; P R Hiebert; H Y Park; D Stefanowicz; A Le; M R Starkey; A Deane; A C Brown; G Liu; J C Horvat; Z A Ibrahim; M B Sukkar; P M Hansbro; C Carlsten; S VanEeden; D D Sin; K M McNagny; D A Knight; J A Hirota Journal: Mucosal Immunol Date: 2015-10-28 Impact factor: 7.313
Authors: T Eleftheriadis; G Pissas; A Karioti; G Antoniadi; S Golfinopoulos; V Liakopoulos; A Mamara; M Speletas; G Koukoulis; I Stefanidis Journal: Hippokratia Date: 2013-04 Impact factor: 0.471