DNA-Mediated Interferon Signature Induction by SLE Serum Occurs in Monocytes Through Two Pathways: A Mechanism to Inhibit Both Pathways
| العنوان: | DNA-Mediated Interferon Signature Induction by SLE Serum Occurs in Monocytes Through Two Pathways: A Mechanism to Inhibit Both Pathways |
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| المؤلفون: | Amit Porat, Eitan Giat, Czeslawa Kowal, Mingzhu He, Myoungsun Son, Eicke Latz, Ilan Ben-Zvi, Yousef Al-Abed, Betty Diamond |
| المصدر: | Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media SA, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, lcsh:Immunologic diseases. Allergy, 0301 basic medicine, media_common.quotation_subject, Immunology, omega-Chloroacetophenone, RAGE (receptor), 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, HMGB1 Protein, Internalization, Receptor, systemic lupus erythematosus (SLE), Original Research, media_common, Chemistry, Monocyte, Pathogen-associated molecular pattern, Receptors, IgG, Pattern recognition receptor, type 1 interferon, receptor for advanced glycation end products (RAGE), Mice, Mutant Strains, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Antibodies, Antinuclear, Immunoglobulin G, Nucleic acid, Female, Interferons, Fc receptor gamma 2a, monocytes, lcsh:RC581-607, Cell-Free Nucleic Acids, DNA, 030215 immunology |
| الوصف: | A primary mechanism for activation of innate immunity is recognition of damage or pathogen associated molecular patterns by pattern recognition receptors (PRRs). Nucleic acid is a damage associated molecular pattern molecule that when internalized into a monocyte and recognized by intracellular nucleic acid sensing toll like receptors will cause production of type 1 interferon. The process by which DNA or RNA is delivered into the cytosol of monocytes in systemic lupus erythematosus remains incompletely understood, and therapeutic approaches to prevent DNA-mediated monocyte activation are needed. We identified two mechanisms for internalization of DNA by monocytes. IgG-bound DNA was internalized by interacting with Fc gamma receptor IIa, while high-mobility group box-1 protein-bound DNA was internalized by interacting with the receptor for advanced glycation end products. Both pathways contribute to an inflammatory phenotype in monocytes exposed to serum from patients with SLE. Moreover, both of these pathways can be inhibited by a pentapeptide, DWEYS, which is a DNA mimetope. In one instance DWEYS directly competes with DNA for antibody binding and in the other DWEYS binds high-mobility group box-1 and blocks its interaction with RAGE. Our data highlight distinct pathways involved in nucleic acid enters monocytes in SLE, and identify a potential therapeutic to prevent nucleic acid internalization in SLE. |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8bb6e0ecc83713bbcc7c255d6cdf47afTest https://doi.org/10.3389/fimmu.2018.02824Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8bb6e0ecc83713bbcc7c255d6cdf47af |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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