Adenosine receptor A2a blockade by caffeine increases IFN-gamma production in Th1 cells from patients with rheumatoid arthritis

• Published in: Scandinavian journal of rheumatology Vol. 51; no. 4; pp. 1 - 283
• Main Authors: Gloyer, L, Golumba-Nagy, V, Meyer, A, Yan, S, Schiller, J, Breuninger, M, Jochimsen, D, Kofler, D M
• Format: Journal Article
• Language: English
• Published: England 04.07.2022
• ISSN: 0300-9742; 1502-7732
• DOI: 10.1080/03009742.2021.1995956

Studies indicate that caffeine uptake may be a risk factor for rheumatoid arthritis (RA), but a definitive link between caffeine consumption and RA has not been established. This study aimed to investigate the interplay between caffeine, adenosine receptor A2a, and interferon-γ (IFN-γ) production in CD4 T cells from RA patients. Peripheral blood mononuclear cells were obtained from the peripheral blood of healthy individuals and patients with RA. CD4  T cells were isolated using the magnetic activated cell sorting technique and cultured in vitro with caffeine or mock control. In addition, adenosine was used as a competitive inhibitor of caffeine. After 48 h, expression of IFN-γ and interleukin-17 (IL-17) was analysed by flow cytometry. Ex vivo expression levels of adenosine receptor A2a were also assessed. Caffeine promoted IFN-γ production in Th1 cells in vitro. Significantly higher concentrations of caffeine were required to increase IFN-γ levels in Th1 cells from healthy individuals compared to Th1 cells from patients with RA. Moreover, ex vivo levels of adenosine receptor A2a expression on CD4  T cells were significantly higher in RA than in healthy individuals. Caffeine-driven IFN-γ production was completely reversed by adenosine, a competitive agonist of adenosine receptor A2a. In contrast to IFN-γ, production of IL-17 was not affected by caffeine. Caffeine promotes IFN-γ production in Th1 cells from RA patients in vitro by competitive inhibition of adenosine receptor A2a. Excessive coffee consumption could contribute to T-cell activation and inflammation in RA.