LSECs express functional NOD1 receptors: A role for NOD1 in LSEC maturation-induced T cell immunity in vitro. (September 2018)

• Record Type: Journal Article
• Authors: Huang, Shunmei; Wu, Jun; Gao, Xiaoyan; Zou, Shi; Chen, Liwen; Yang, Xilang; Sun, Chan; Du, Yanqin; Zhu, Bin; Li, Jia; Yang, Xuecheng; Feng, Xuemei; Wu, Chunchen; Shi, Chunwei; Wang, Baoju; Lu, Yinping; Liu, Jia; Zheng, Xin; Gong, Feili; Lu, Mengji; Yang, Dongliang
• Is Part Of: Molecular immunology. Volume 101(2018:Sep.)
• Page Start: 167
• Page End: 175
• Publication Date: 2018-09
• Subjects: HBV Hepatitis B virus -- LSECs liver sinusoidal endothelial cells -- NLR NOD-like receptors -- TLR toll-like receptors -- DAP diaminopimelic acid -- RIPK2 receptor-interacting serine-threonine protein kinase 2 -- NF-κB nuclear factor-κB -- MAPK mitogen-activated protein kinase -- IFN-α alpha interferon -- PRR pattern recognition receptor -- MAMPs microbial-associated molecular patterns -- PAMPs pathogen-associated molecular patterns -- DAMPs damage-associated molecular patterns -- HI hydrodynamic injection -- NOD nucleotide-binding oligomerization domain -- IFN interferon -- IL interleukin -- TNF-α tumour necrosis factor alpha -- APCs antigen-presenting cells; Innate immunity -- NOD1 ligand -- LSEC -- Hepatitis B -- T cell response; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2018.06.002
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: LSECs stimulated with MDP only can induce the upregulation of the co-inhibitory molecule PD-L1. DAP stimulation in vitro could promote LSEC maturation and activate HBV-specific T cell responses. T cells pre-primed by DAP-treated LSECs can inhibit HBV expression and replication in vivo. These results are of particular relevance for the regulation of the local innate immune response against HBV infections. Abstract: 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.