Intravenous delivery of HIV-based lentiviral vectors preferentially transduces F4/80+ and Ly-6C+ cells in spleen, important target cells in autoimmune arthritis
| العنوان: | Intravenous delivery of HIV-based lentiviral vectors preferentially transduces F4/80+ and Ly-6C+ cells in spleen, important target cells in autoimmune arthritis |
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| المؤلفون: | Miranda B. Bennink, Wim B. van den Berg, Eline A. Vermeij, Michael Kracht, Ben T van den Brand, Claire E J Waterborg, Onno J. Arntz, Fons A. J. van de Loo |
| المصدر: | PLoS One, 8, 2 PLoS One, 8 PLoS ONE, Vol 8, Iss 2, p e55356 (2013) PLoS ONE |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Gene Expression, Arthritis, Autoimmunity, medicine.disease_cause, Mice, T-Lymphocyte Subsets, Transduction, Genetic, Synovial Fluid, Antigens, Ly, Transgenes, Multidisciplinary, T Cells, Genomics, Gene Therapy, MAP Kinase Kinase Kinases, Infection and autoimmunity Auto-immunity, transplantation and immunotherapy [NCMLS 1], medicine.anatomical_structure, Mice, Inbred DBA, Injections, Intravenous, Cytokines, Medicine, Immunotherapy, Inflammatory and Psoriatic Arthritis, medicine.symptom, Research Article, Immune Cells, Science, Immunology, Genetic Vectors, Green Fluorescent Proteins, Antigen-Presenting Cells, Rheumatoid Arthritis, Spleen, Inflammation, Biology, Proinflammatory cytokine, Immunomodulation, Genomic Medicine, Rheumatology, Antigen, medicine, Animals, Antigen-presenting cell, Collagen Type II, Clinical Genetics, Cluster of differentiation, Immunity, HIV, Dendritic Cells, medicine.disease, Antigens, Differentiation, Arthritis, Experimental, Immune System |
| الوصف: | Contains fulltext : 118684.pdf (Publisher’s version ) (Open Access) Antigen presenting cells (APCs) play an important role in arthritis and APC specific gene therapeutic targeting will enable intracellular modulation of cell activity. Viral mediated overexpression is a potent approach to achieve adequate transgene expression levels and lentivirus (LV) is useful for sustained expression in target cells. Therefore, we studied the feasibility of lentiviral mediated targeting of APCs in experimental arthritis. Third generation VSV-G pseudotyped self-inactivating (SIN)-LV were injected intravenously and spleen cells were analyzed with flow cytometry for green fluorescent protein (GFP) transgene expression and cell surface markers. Collagen-induced arthritis (CIA) was induced by immunization with bovine collagen type II in complete Freund's adjuvant. Effect on inflammation was monitored macroscopically and T-cell subsets in spleen were analyzed by flow cytometry. Synovium from arthritic knee joints were analyzed for proinflammatory cytokine expression. Lentiviruses injected via the tail vein preferentially infected the spleen and transduction peaks at day 10. A dose escalating study showed that 8% of all spleen cells were targeted and further analysis showed that predominantly Ly6C+ and F4/80+ cells in spleen were targeted by the LV. To study the feasibility of blocking TAK1-dependent pathways by this approach, a catalytically inactive mutant of TAK1 (TAK1-K63W) was overexpressed during CIA. LV-TAK1-K63W significantly reduced incidence and arthritis severity macroscopically. Further histological analysis showed a significant decrease in bone erosion in LV-TAK1-K63W treated animals. Moreover, systemic Th17 levels were decreased by LV-TAK1-K63W treatment in addition to diminished IL-6 and KC production in inflamed synovium. In conclusion, systemically delivered LV efficiently targets monocytes and macrophages in spleen that are involved in autoimmune arthritis. Moreover, this study confirms efficacy of TAK1 targeting in arthritis. This approach may provide a valuable tool in targeting splenic APCs, to unravel their role in autoimmune arthritis and to identify and validate APC specific therapeutic targets. |
| وصف الملف: | application/pdf |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0753cc338c73478c3837279ca63dd1cd https://hdl.handle.net/2066/118684 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0753cc338c73478c3837279ca63dd1cd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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