LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

Abstract

BackgroundThe disease burden caused by chronic hepatitis B virus (HBV) infection is still heavy, and the current treatment scheme has not achieved a complete cure. Changes in natural and adaptive immunity usually accompany chronic HBV infection. As a marker expressed on dendritic cells (DCs), whether lysosome-associated membrane glycoprotein 3 (LAMP3) participates in chronic HBV infection deserves further analysis.MethodsWe retrieved chronic HBV infection transcriptional information from the Gene Expression Omnibus (GEO) database. The LAMP3 expression in the liver of patients with chronic hepatitis B (CHB) was analyzed in three GEO datasets and confirmed in our validation cohort (27 patients with CHB). Differentially expressed genes were obtained from one CHB cohort by comparing LAMP3high and LAMP3low expression subgroups. These genes underwent Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis to decipher the influence of LAMP3 on the biological process and immunity changes in HBV infection. Furthermore, we investigated the potential relationship between LAMP3 levels, the abundance of infiltrating immune cells, and liver dysfunction.ResultsCompared to healthy controls, LAMP3 expression was upregulated in the transcriptional profiles of the liver in patients with CHB. The high LAMP3 expression was related to T cell activation and the chemokine signaling pathway. The LAMP3 gene was positively linked to marker sets of infiltrating activated regulatory T cells (Treg), T cell exhaustion, monocytes, and DCs. Moreover, CHB patients with high LAMP3 expression had unfavorable liver dysfunction.ConclusionsLAMP3 is a gene related to HBV infection, which might be involved in HBV infection by regulating T cell activation and adaptive immune response.

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“…Upregulation of DC-LAMP was associated with T cell activation and adaptive immune regulation. There was a close relationship between the expression of the DC-LAMP TGF-β gene [ 10 ], which is an important factor leading to the intensification of fibrosis processes [ 42 ].…”

“…DC-LAMP + DCs express multiple ligands to interact with receptors on T cells, possibly being the most active immune regulators of lymphocytes. A close relationship between T reg cell markers (i.e., transforming growth factor β, TGF-β) and DC-LAMP mRNA levels was shown [ 10 ]. Dendritic-cell-specific intercellular-adhesion-molecule-3-grabbing non-integrin (DC-SIGN or CD209) is a C-type lectin receptor that is selectively expressed on DCs and is considered to be another marker of their maturity [ 11 , 12 ].…”

Traditional Chinese medicines and natural products targeting immune cells in the treatment of metabolic-related fatty liver disease

“…In particular, it has been shown that DCs accumulate in the liver of patients with MAFLD and produce pro-inflammatory cytokines (such as IL-1, TNF-α, IL-12, and IL-18) that drive the recruitment and activation of other immune cells, such as macrophages, T cells, and neutrophils (Heier et al, 2017;Yang et al, 2021). Moreover, DCs also contribute to the activation and differentiation of regulatory T (Treg) cells, which play a critical role in suppressing immune responses and maintaining immune tolerance (Wang et al, 2023). Dysregulation of DC function in MAFLD may hinder the induction of Treg cells and promote inflammation and fibrosis.…”