Apigenin Modulates Dendritic Cell Activities and Curbs Inflammation Via RelB Inhibition in the Context of Neuroinflammatory Diseases

Neuroinflammation leads to tissue injury causing many of the clinical symptoms of Multiple Sclerosis, an autoimmune disorder of the central nervous system (CNS). While T cells, specifically T(h)1 and T(h)17 cells, are the ultimate effectors of this disease, dendritic cells (DCs) mediate T cell polarization, activation, etc. In our previous study, Apigenin, a natural flavonoid, has been shown to reduce EAE disease severity through amelioration of demyelination in the CNS as well as the sequestering of DCs and other myeloid cells in the periphery. Here, we show that Apigenin exerts its effects possibly through shifting DC modulated T cell responses from T(h)1 and T(h)17 type towards T(reg)directed responses evident through the decrease in T-bet, IFN-gamma (T(h)1),IL-17 (T(h)17) and increase in IL-10, TGF-beta and FoxP3 (T-reg) expression in cells from both normal human donors and EAE mice. RelB, an NF-kappa beta pathway protein is central to DC maturation, its antigen presentation capabilities and DC-mediated T cell activation. Apigenin reduced mRNA and protein levels of RelB and also reduced its nuclear translocation. Additionally, siRNA-mediated silencing of RelB further potentiated the RelB-mediated effects of Apigenin thus confirming its role in Apigenin directed regulation of DC biology. These results provide key information about the molecular events controlled by Apigenin in its regulation of DC activity marking its potential as a therapy for neuroinflammatory disease.

Automated summary

Apigenin reduces EAE severity by shifting T cell responses from T(h)1 and T(h)17 to T(reg) type through modulation of DC activity. This is achieved by decreasing T-bet, IFN-gamma (T(h)1), IL-17 (T(h)17) and increasing IL-10, TGF-beta, and FoxP3 (T-reg) expression.