Figure 1.

A simplified scheme of imbalanced immune response, connecting the cellular and cytokines imbalances with the activation of IL-17 axis and the progression of NAFLD. Metabolic disorders lead to immune imbalances in the peripheral blood and/or in the liver that are expressed at the cellular level by Th17/Treg imbalance and by the dominance of neutrophil over lymphocytes. These are reflected in imbalanced soluble factors with the dominance of pro-inflammatory and profibrotic over the anti-inflammatory and antifibrotic, which culminates in the Th17/IL-17 axis hyperactivation. In the liver, these imbalances are responsible for the recruitment and organ infiltration by neutrophil (102, 103), for increased hepatic gene expression of Th17-related cytokines (IL-17, IL-21, and IL-23) (29), resulting in steatohepatitis and fibrosis. The extra-hepatic effect, is increased production and release of neutrophils (101), and greater polarization to Th17 response, increasing further cellular imbalances, and acting as a feedback loop. Th17-secreted cytokines are listed in red.