Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling
| Autor: | 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 |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
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 |
| Zdroj: | Proceedings of the National Academy of Sciences. 106:20423-20428 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0910371106 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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