Citation

Selective inhibition of T cells has been implied to prevent and/or treat autoimmune and inflammatory diseases. Some food compounds that have such immune-modulating functions may serve as nutritional approach to this purpose. In this study we chose naringenin, a citrus fruits-derived compound with anti-inflammatory property, to test this possibility. In this in vitro study, we stimulated mouse T cells with anti-CD3/CD28 (polyclonal TCR activation) or autoantigen MOG3555 in the presence of naringenin. We found that naringenin does-dependently suppressed anti-CD3/CD28 and MOG3555-induced T cell proliferation, production of T cell cytokines IFN-, IL-17, IL-6, and TNF-. We further showed that inhibited T cell proliferation was associated with T cell cycle arrest at G0/G1 phase, which was in turn related to delayed degradation of the cyclin-dependent kinase inhibitor p27kip1 and the down-regulation of retinoblastoma protein phosphorylation in activated T cells. Finally, it was revealed that all these T cell-suppressive effects might be related to naringenin’s interference with IL-2/IL-2R-mediated signaling pathway and STAT5 phosphorylation in activated T cells. Our results confirmed T cell-suppressive activity of naringenin previously reported by us and others, but for the first time it was shown that the working mechanism may involve its ability to modulate cell cycle progression, cell cycle-related proteins, and IL-2/IL-2R signaling pathway. Together these results further support proposed potential of naringenin being a preventive/therapeutic agent in T-cell mediated autoimmune inflammatory disorders.