Cyanidin restores Th17/Treg balance and inhibits T follicular helper cell differentiation via modulation of ROCK2 signaling in an experimental model of rheumatoid arthritis

Disturbed Th17/Treg balance is a critical pathological event in the disease progression of rheumatoid arthritis (RA). Recently, emerging studies have demonstrated that CD4 + T helper follicular (Tfh) cells exacerbates the pathogenic manifestations of RA. Contrarily, our previous report has shown that cyanidin, a flavonoid compound, attenuates disease severity of RA. Howbeit, this study investigated the therapeutic efficacy of cyanidin in relation to Th17/Treg balance and pathogenic Tfh cells in RA. Onto results, cyanidin inhibited increased Th17 cell differentiation and reciprocally improved FoxP3 + Treg cells both in-vivo and in-vitro. Concomitantly, cyanidin abated the detrimental effects of IL-17 via restoration of IL-10 secretion in adjuvant induced arthritic (AIA) rats. Furthermore, cyanidin reduced Tfh cells proportion and IgG levels in AIA rats, thus rectifying Tfh and follicular regulatory T (Tfr) cell ratio. Mechanistically, the restoring effect of cyanidin was associated with blunted activation of ROCK2/STAT3 signaling axis and reciprocal increase in the level of STAT-5 activity. Notwithstanding, cyanidin therapeutic efficacy correlated with specific oral ROCK2 inhibitor KD025 in-vitro. Collectively, these results demonstrate a dual promising therapeutic role of cyanidin via regulating Th17/Treg ratio and Tfh cell differentiation in an experimental model of RA.