Journal
MOLECULAR IMMUNOLOGY
Volume 101, Issue -, Pages 167-175Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2018.06.002
Keywords
Innate immunity; NOD1 ligand; LSEC; Hepatitis B; T cell response
Categories
Funding
- National Natural Science Foundation of China [81461130019, 81672022, 81001313]
- National Major Science and Technology Project for Infectious Diseases of China [2008ZX10002-011, 2012ZX10004503, 2013ZX10002001-001-006]
- International Science & Technology Cooperation Program of China [2011DFA31030]
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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-kappa B and MAP kinases and upregulated the expression of chemokines (CXCL2/9, CCL2/7/8) and cytokines (IFN-gamma, TNF-alpha and IL-2). Pretreatment of LSECs with DAP induced significantly increased IFN-gamma and IL-2-production by HBV-stimulated CD8(+) T cells primed by DAPtreated 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.
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