Geranylgeranyl pyrophosphate amplifies T _reg differentiation via increased IL‐2 expression to ameliorate DSS‐induced colitis

Blocking the mevalonate pathway for cholesterol reduction by using statin may have adverse effects including statin-induced colitis. Moreover, one of predisposing factors colitis is an imbalanced CD4+ T cell, which can be observed on complete deletion HMG-CoA reductase (HMGCR), a target statins. In this study, we inquired geranylgeranyl pyrophosphate (GGPP) responsible maintaining T-cell homeostasis. Following dextran sulfate sodium (DSS)-induced colitis, simvastatin increased severity disease, while cotreatment with GGPP, but not cholesterol, reversed disease magnitude. GGPP ameliorated DSS-induced increasing Treg cells. amplified differentiation through IL-2/STAT 5 signaling. prenylated Ras protein, prerequisite extracellular signal-regulated kinase (ERK) activation, leading to IL-2 production. Higher dose simvastatin-increased cells, capacity suppress inflammatory cells and were generated IL-2/STAT5 signaling, production prenylation activation Ras/ERK pathway.