Liver sinusoidal endothelial cells (LSECs) are organ resident APCs capable of antigen presentation and subsequent tolerization of T cells under physiological conditions. In this study, we investigated whether LSEC pretreatment with NOD-like receptor (NLR) agonists can switch the cells from a tolerogenic to an immunogenic state and promote the development of T cell immunity. LSECs constitutively express NOD1, NOD2 and RIPK2. Stimulation of LSECs with DAP induced the activation of NF-κB and MAP kinases and upregulated the expression of chemokines (CXCL2/9, CCL2/7/8) and cytokines (IFN-γ TNF-α and IL-2). Pretreatment of LSECs with DAP induced signiﬁcantly increased IFN-γ and IL-2-production by HBV-stimulated CD8 + T cells primed by DAP-treated LSECs. Consistently, a signiﬁcant reduction in the HBV DNA and HBsAg level occurred in mice receiving T cells primed by DAP-treated LSECs. MDP stimulation had no impact on LSECs or HBV-stimulated CD8 + T cells primed with MDP-treated LSECs except for the upregulation of PD-L1. DAP stimulation in vitro could promote LSEC maturation and activate HBV-specific T cell responses. These results are of particular relevance for the regulation of the local innate immune response against HBV infections.
Huang, S., Wu, J., Gao, X., Zou, S., Chen, L., Yang, X., … Yang, D. (2018). LSECs express functional NOD1 receptors: A role for NOD1 in LSEC maturation-induced T cell immunity in vitro. Molecular Immunology, 101, 167–175. https://doi.org/10.1016/j.molimm.2018.06.002