Immune functions of liver sinusoidal endothelial cells

Immune regulation in the liver is biased towards tolerance rather than immunity. Antigen‐presenting LSEC induce tolerance in CD8 T cells and rely on crosstalk leading to exchange of tolerogenic signals through B7‐H1 and PD1. We investigated whether LSEC underwent functional maturation. We found that LSEC express pattern recognition receptors (PRR), which upon activation cause increased expression of CD106, but there was no functional maturation of LSEC. Comparing the gene expression profile of LPS‐stimulated DC with LSEC, it became evident that sentinel function in LSEC elicited a fundamentally different gene expression program. So we next investigated the influence of a viral infection (MCMV). Although LSEC were infected and allowed for viral gene expression, IFNb release prevented viral replication. Viral infection improved T cell stimulation and caused phenotypic maturation of LSEC that now elicited full CD8 effector T cell differentiation in the absence of costimulatory molecules. Bioinformatic analysis of the gene expression profile revealed that complex regulation of gene expression was correlated with immunogenic maturation. Our results identify a novel principle of CD8 T cell differentiation in the absence of well‐known costimulatory signals and will thus shed new light on development of organ‐specific autoimmunity.