Microvesicles in active lupus nephritis show Toll-like receptor 9-dependent co-expression of galectin-3 binding protein and double-stranded DNA
| Autor: | Niclas Stefan Rasmussen, Søren Jacobsen, Claus Henrik Nielsen, Christoffer Tandrup Nielsen |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Immunology Lupus nephritis Peripheral blood mononuclear cell law.invention Flow cytometry Young Adult 03 medical and health sciences 0302 clinical medicine Antigens Neoplasm Cell-Derived Microparticles immune system diseases law Gardiquimod Biomarkers Tumor medicine Humans Lupus Erythematosus Systemic Immunology and Allergy skin and connective tissue diseases Receptor Cells Cultured medicine.diagnostic_test Chemistry Interferon-alpha TLR9 DNA Original Articles Middle Aged Flow Cytometry medicine.disease Lupus Nephritis Molecular biology Microvesicles 030104 developmental biology Oligodeoxyribonucleotides Toll-Like Receptor 9 Leukocytes Mononuclear Recombinant DNA Female 030215 immunology |
| Zdroj: | Clin Exp Immunol |
| ISSN: | 1365-2249 0009-9104 |
| Popis: | Summary Circulating microvesicles (MVs) from patients with systemic lupus erythematosus (SLE) express the type 1 interferon (IFN)-inducible protein galectin-3 binding protein (G3BP), which may enhance their deposition in the glomerular basement membrane. The release of G3BP-expressing MVs from normal peripheral blood mononuclear cells (PBMCs) is induced by Toll-like receptor 9 (TLR-9) ligands, and these vesicles contain autoantibody-accessible double-stranded DNA (dsDNA). This study compares the release of MVs expressing G3BP and dsDNA from PBMCs derived from SLE patients with or without active lupus nephritis (LN) and from healthy donors, and taps further into the potential dependency on IFN-α for their generation and impacts of TLR-7/TLR-9 co-stimulation. PBMCs from 10 healthy donors and 12 SLE patients, six of whom had active LN at study inclusion, were stimulated in-vitro with recombinant human IFN-α and the TLR-9 agonists oligodeoxynucleotide (ODN)2216 or ODN2395 alone or in combination with the TLR-7 agonist gardiquimod. MVs in the supernatants were subsequently isolated by differential centrifugation and their expression of G3BP and dsDNA was quantified by flow cytometry. Stimulation with ODN2395 significantly increased the release of MVs co-expressing G3BP and dsDNA from PBMCs isolated from healthy donors and SLE patients. The expression of G3BP on individual MVs and the proportion of G3BP and dsDNA double-positive MVs released were increased in active LN patients. Neither co-stimulation with gardiquimod nor with the IFN-α inhibitor IN-1 had any effect on the MV release induced by ODN2395. In conclusion, the TLR-9-mediated inducibility of MVs co-expressing G3BP and dsDNA is increased in SLE patients with active LN. |
| Databáze: | OpenAIRE |
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