Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Pflegerl, P; Vesely, P; Hantusch, B; Schlederer, M; Zenz, R; Janig, E; Steiner, G; Meixner, A; Petzelbauer, P; Wolf, P; Soleiman, A; Egger, G; Moriggl, R; Kishimoto, T; Wagner, EF; Kenner, L.
Epidermal loss of JunB leads to a SLE phenotype due to hyper IL-6 signaling.
Proc Natl Acad Sci U S A. 2009; 106(48):20423-20428
Doi: 10.1073/pnas.0910371106
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- Co-authors Med Uni Graz
- Janig Elke
- Kenner Lukas
- Vesely Paul
- Wolf Peter
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- Abstract:
- 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(Deltaep)) 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(Deltaep) 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 alpha-IL-6 receptor antibody therapy for treatment of SLE.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Chromatin Immunoprecipitation -
- Crosses, Genetic -
- Enzyme-Linked Immunosorbent Assay -
- Epidermis - metabolism
- Fluorescent Antibody Technique, Direct -
- Gene Expression Regulation - physiology
- Granulocyte Colony-Stimulating Factor - metabolism
- Humans -
- Interleukin-6 - metabolism Interleukin-6 - secretion
- Keratinocytes - metabolism
- Luciferases -
- Lupus Erythematosus, Systemic - metabolism Lupus Erythematosus, Systemic - pathology
- Mice -
- Mice, Transgenic -
- Microscopy, Electron -
- Proto-Oncogene Proteins c-jun - deficiency Proto-Oncogene Proteins c-jun - metabolism
- Find related publications in this database (Keywords)
- epidermis
- IL-6R
- systemic lupus erythematosus