Impaired TLR9 responses in B cells from patients with systemic lupus erythematosus
| Autor: | Vincent, Gies, Jean-Nicolas, Schickel, Sophie, Jung, Aurélie, Joublin, Salomé, Glauzy, Anne-Marie, Knapp, Anne, Soley, Vincent, Poindron, Aurélien, Guffroy, Jin-Young, Choi, Jacques-Eric, Gottenberg, Jennifer H, Anolik, Thierry, Martin, Pauline, Soulas-Sprauel, Eric, Meffre, Anne-Sophie, Korganow |
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| Přispěvatelé: | Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Yale University School of Medicine, Centre National de Référence pour les Maladies Auto-immunes Rares [CHU Strasbourg] (RESO), University of Rochester Medical Center (URMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Yale School of Medicine [New Haven, Connecticut] (YSM), univOAK, Archive ouverte |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male [SDV.IMM] Life Sciences [q-bio]/Immunology Autoimmune diseases Antigens CD19 Primary Cell Culture Immunology lcsh:Medicine chemical and pharmacologic phenomena Autoimmunity Young Adult immune system diseases Immune Tolerance Humans Lupus Erythematosus Systemic Sciences du Vivant [q-bio]/Immunologie skin and connective tissue diseases Cells Cultured Aged Aged 80 and over B-Lymphocytes B cells lcsh:R hemic and immune systems Dendritic Cells Middle Aged Up-Regulation Oligodeoxyribonucleotides Toll-Like Receptor 9 Cytokines [SDV.IMM]Life Sciences [q-bio]/Immunology Female Receptors Complement 3d Research Article |
| Zdroj: | JCI Insight JCI Insight, American Society for Clinical Investigation, 2018, 3 (5), ⟨10.1172/jci.insight.96795⟩ JCI Insight, 2018, 3 (5), ⟨10.1172/jci.insight.96795⟩ JCI Insight, Vol 3, Iss 5 (2018) |
| ISSN: | 2379-3708 |
| Popis: | B cells play a central role in systemic lupus erythematosus (SLE) pathophysiology but dysregulated pathways leading to a break in B cell tolerance remain unclear. Since Toll-like receptor 9 (TLR9) favors the elimination of autoreactive B cells in the periphery, we assessed TLR9 function in SLE by analyzing the responses of B cells and plasmacytoid dendritic cells (pDCs) isolated from healthy donors and patients after stimulation with CpG, a TLR9 agonist. We found that SLE B cells from patients without hydroxychloroquine treatment displayed defective in vitro TLR9 responses, as illustrated by the impaired upregulation of B cell activation molecules and the diminished production of various cytokines including antiinflammatory IL-10. In agreement with CD19 controlling TLR9 responses in B cells, decreased expression of the CD19/CD21 complex on SLE B cells was detected as early as the transitional B cell stage. In contrast, TLR7 function was preserved in SLE B cells, whereas pDCs from SLE patients properly responded to TLR9 stimulation, thereby revealing that impaired TLR9 function in SLE was restricted to B cells. We conclude that abnormal CD19 expression and TLR9 tolerogenic function in SLE B cells may contribute to the break of B cell tolerance in these patients. |
| Databáze: | OpenAIRE |
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