Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling
| العنوان: | Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling |
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| المؤلفون: | Gerda Egger, Afschin Soleiman, Paul Vesely, Michaela Schlederer, Pamina Pflegerl, Rainer Zenz, Richard Moriggl, Peter Petzelbauer, Tadamitsu Kishimoto, Erwin F. Wagner, Brigitte Hantusch, Arabella Meixner, Lukas Kenner, Günter Steiner, Elke Janig, Peter Wolf |
| المصدر: | Proceedings of the National Academy of Sciences. 106:20423-20428 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Keratinocytes, Chromatin Immunoprecipitation, Proto-Oncogene Proteins c-jun, JUNB, medicine.medical_treatment, Transgene, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, Biology, Mice, immune system diseases, hemic and lymphatic diseases, Granulocyte Colony-Stimulating Factor, medicine, Animals, Humans, Lupus Erythematosus, Systemic, Luciferases, skin and connective tissue diseases, Interleukin 6, STAT3, Crosses, Genetic, Autoimmune disease, Multidisciplinary, Lupus erythematosus, Systemic lupus erythematosus, Interleukin-6, Biological Sciences, medicine.disease, Microscopy, Electron, Cytokine, Gene Expression Regulation, Fluorescent Antibody Technique, Direct, Immunology, biology.protein, Epidermis |
| الوصف: | Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting various tissues. Involvement of B and T cells as well as increased cytokine levels have been associated with disease manifestation. Recently, we demonstrated that mice with epidermal loss of JunB (JunB Δep ) develop a myeloproliferative syndrome (MPS) due to high levels of G-CSF which are secreted by JunB-deficient keratinocytes. In addition, we show that JunB Δep mice develop a SLE phenotype linked to increased epidermal interleukin 6 (IL-6) secretion. Intercrosses with IL-6-deficient mice could rescue the SLE phenotype. Furthermore, we show that JunB binds to the IL-6 promoter and transcriptionally suppresses IL-6. Facial skin biopsies of human SLE patients similarly revealed low JunB protein expression and high IL-6, activated Stat3, Socs-1, and Socs-3 levels within lupus lesions. Thus, keratinocyte-induced IL-6 secretion can cause SLE and systemic autoimmunity. Our results support trials to use α-IL-6 receptor antibody therapy for treatment of SLE. |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0910371106 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::016d6511685e8bb091c77ed01e67d53e https://doi.org/10.1073/pnas.0910371106 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....016d6511685e8bb091c77ed01e67d53e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.0910371106 |