Systemic gene transfer of binding immunoglobulin protein (BiP) prevents disease progression in murine collagen-induced arthritis

Abstract

SummaryRecombinant human binding immunoglobulin protein (BiP) has previously demonstrated anti-inflammatory properties in multiple models of inflammatory arthritis. We investigated whether these immunoregulatory properties could be exploited using gene therapy techniques. A single intraperitoneal injection of lentiviral vector containing the murine BiP (Lenti-mBiP) or green fluorescent protein (Lenti-GFP) transgene was administered in low-or high-dose studies during early arthritis. Disease activity was assessed by visual scoring, histology, serum cytokine and antibody production measured by cell enzyme-linked immunosorbent assay (ELISA) and ELISA, respectively. Lentiviral vector treatment caused significant induction of interferon (IFN)-γ responses regardless of the transgene; however, further specific effects were directly attributable to the BiP transgene. In both studies Lenti-mBiP suppressed clinical arthritis significantly. Histological examination showed that low-dose Lenti-mBiP suppressed inflammatory cell infiltration, cartilage destruction and significantly reduced pathogenic anti-type II collagen (CII) antibodies. Lenti-mBiP treatment caused significant up-regulation of soluble cytotoxic T lymphocyte antigen

Effect of Binding Immunoglobulin Protein On Induction of Regulatory B Cells With Killer Phenotype During Inflammation and Disease

“…Additionally, this upregulation was associated with increased proliferation of synoviocyte cells and progressive pathogenesis of RA in synoviocytes. This suggested that T cell surface BiP can modulate pro-inflammatory responses in synoviocytes Interestingly, transfection of the BiP gene into murine and human PBMC samples using a viral vector has been evaluated as having the same anti-inflammatory effects as stimulating arthritis inflammation with synthesised proteins in collagen [ 55 ]. Supporting evidence of extracellular BiP binding to immune cells was shown in a study by Tang et al ., (2016) where BiP induced the development of regulatory B cells in murine samples and worked in synergy with CD40 to suppress proliferation of T cells [ 29 ].…”

Emerging Trends in Abdominal Wall Reinforcement: Bringing Bio‐Functionality to Meshes

“…To tackle this problem, in vitro re‐programming of autologous cells using specific growing conditions prior to re‐transplantation with PP mesh has been conducted on patients and revealed beneficial outcomes compared to conventional acellular mesh therapy . In addition, in situ re‐stimulation of the patient's own cells by local gene delivery from activated mesh would deserve more attention in the future, as it has already shown remarkable results in other collagen expression‐related diseases …”