**4.2 Liver sinusoidal endothelial cells**

Liver sinusoidal endothelial cells (LSECs) are an important part of the reticuloendothelial system. They are highly specialized and form the lining of the hepatic sinusoids. Their characteristic morphology (abundant fenestrae) and the permanent exposition to the blood flow permit them to filter out blood antigens. From an immunological viewpoint LSECs are liver-resident antigen-presenting cells that might be considered as bridge between the innate and adaptive immunity. It is evidenced by the expression of TLRs and RIGs, which under stimulation, turn on the production of proinflammatory cytokines, upregulation of costimulatory molecules and release of cytokines, that affect T cells [13, 37]. In parallel, LSECs may present antigens to T cells although not being professional APCs as shown by the expression of MHC class I on the LSECs surface [15]. The question about MHC

class II expression is still not well clarified, although under specific conditions, LSECs may present antigens to CD4+ T cells inducing immune tolerance [38] . LSEC actively participate in the induction of tolerance. For example, in naïve CD8+ T cells, the cognate interaction triggers the expression of co-inhibitory B7-H1 but not the co-stimulatory CD80/86 molecules exclusively on LSEC but not DC, which together with increased costimulation via CD28 is critical for the induction of CD8+ T cell tolerance by LSEC [39].
