Figure 3.

Oxidative stress in the progression of NASH. In the first instance, lipotoxicity and intestinal dysbiosis can produce an environment of oxidative stress, which contributes to the development of fibrosis through the activation of Kupffer cells (KCs) and hepatic stellate cells (HSCs), also, this stress generates a response from both the innate and adaptive immune system, through the production of oxidation-specific epitopes (OSEs) favoring the activation of KCs with the further released of pro-inflammatory cytokines and chemokines such as TNFα, IFNγ, PGE2, CCL, IL-1α, IL-1β, ROS, NO, TGFβ and C3ar1 activating natural killer T cells (NKT) and HSCs. In addition, KCs will enhance the differentiation of both T and B cells. CD4+ T cells will polarize into Th1 and Th17 cells promoting the activation of macrophages and establishing lymphocytic infiltrates aggravating the pro-inflammatory state. On the other hand, CD45+ B cells will express anti-OSE IgG enhancing the activation of CD4+ T cells.