Figure 1.

The contribution of DCs and macrophages to the pathomechanism of liver fibrosis and NASH. Liver injury triggers the activation of Kuppfer cells, the resident macrophage population of the liver. Their activation leads to the release of inflammatory mediators and chemokines such as TNF, IL-1β, and CCL2. This is followed by the recruitment of various immune cells involving inflammatory monocytes and DCs. The Ly6C^hi monocytes differentiate into M1 CCR9⁺iNOS⁺ macrophages, and together with DCs in the progression phase of liver injury, act in a pro-inflammatory manner and perpetuate inflammation. Some DCs, possibly the LL-DCs, seem to inhibit liver steatohepatitis and protect liver damage. In resolution, the Ly6C^low restorative macrophages together with MMP9⁺ DCs promote fibrolysis and the restoration of normal tissue architecture. HMGB-1, high mobility group box-1 protein; HSC, hepatic stellate cells; KC, Kupffer cells; LL-DC, low lipid containing DCs; LSEC, liver sinusoidal endothelial cells.