**4.3 Kupffer cells**

Kupffer cells (KCs) are particular subset of macrophages, settled in the liver. They represent appr. 35% of the non-parenchymal liver cells and 90% of all tissue macrophages [40]. They are located in the sinusoids, thus being systematically exposed to gut-derived antigens, circulating immune cells and pathogens. The principle function of KCs is pathogen killing. However, KCs are armed with scavenger receptors, TLRs, complement receptors and antibody receptors, secrete cytokines and chemokines and express broad range of receptor molecules [41]. Thus, KCs not only participate in antimicrobial killing, but also are an active player in the immune network. Their primary function is the antigen presentation. They express MHC class I and class II molecules which together with other costimulatory molecules activate T cells. In healthy conditions, KCs promote immune tolerance in several ways – lower expression of MHC class II, B7–1, B7–2, CD40, PD-1/PD-1 L and possible involvement of IL-10, nitric oxide, TGF-b [38, 42]. Other mechanisms include the ability of KCs to absorb and clear alloreactive antibodies in liver transplantation [43]. Conversely, when stimulated (through TLRs for ex.), KCs become potent activators of T cells and NK cells [44]. In animal models, depletion of graft Kupffer cells was beneficial for the graft acceptance [45]. The double sword performance of KCs needs to be investigated in details, especially in humans. In any case, the current knowledge clearly indicates the KCs impact heavily on the reactivity of the liver immune system.
