Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Singh, TP; Schön, MP; Wallbrecht, K; Michaelis, K; Rinner, B; Mayer, G; Schmidbauer, U; Strohmaier, H; Wang, XJ; Wolf, P.
8-methoxypsoralen plus ultraviolet A therapy acts via inhibition of the IL-23/Th17 axis and induction of Foxp3+ regulatory T cells involving CTLA4 signaling in a psoriasis-like skin disorder.
J Immunol. 2010; 184(12): 7257-7267.
Doi: 10.4049/jimmunol.0903719
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- Führende Autor*innen der Med Uni Graz
- Singh Tej Pratap
- Wolf Peter
- Co-Autor*innen der Med Uni Graz
- Rinner Beate
- Strohmaier Heimo
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- Abstract:
- To elucidate the molecular action of 8-methoxypsoralen plus UVA (PUVA), a standard dermatological therapy, we used K5.hTGF-beta1 transgenic mice exhibiting a skin phenotype and cytokine abnormalities with strong similarities to human psoriasis. We observed that impaired function of CD4+CD25+ regulatory T cells (Tregs) and increased cytokine levels of the IL-23/Th17 pathway were responsible for the psoriatic phenotype in this mouse model. Treatment of K5.hTGF-beta1 transgenic mice with PUVA suppressed the IL-23/Th17 pathway, Th1 milieu, as well as transcription factors STAT3 and orphan nuclear receptor RORgammat. PUVA induced the Th2 pathway and IL-10-producing CD4+CD25+Foxp3+Tregs with disease-suppressive activity that was abolished by anti-CTLA4 mAb treatment. These findings were paralleled by macroscopic and microscopic clearance of the diseased murine skin. Anti-IL-17 mAb treatment also diminished the psoriatic phenotype of the mice. This indicated that both induced Tregs involving CTLA4 signaling and inhibition of the IL-23/Th17 axis are central for the therapeutic action of PUVA.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antigens, CD - drug effects
- CTLA-4 Antigen -
- Cell Separation -
- Disease Models, Animal -
- Enzyme-Linked Immunosorbent Assay -
- Flow Cytometry -
- Fluorescent Antibody Technique -
- Forkhead Transcription Factors - drug effects
- Humans -
- Immunoassay -
- Immunohistochemistry -
- Interleukin-17 - radiation effects
- Interleukin-23 - drug effects
- Methoxsalen - administration and dosage
- Mice -
- Mice, Transgenic -
- Photosensitizing Agents - administration and dosage
- Phototherapy -
- Psoriasis - immunology
- Reverse Transcriptase Polymerase Chain Reaction -
- Signal Transduction - drug effects
- T-Lymphocyte Subsets - drug effects
- T-Lymphocytes, Regulatory - drug effects
- Transforming Growth Factor beta - genetics
- Ultraviolet Rays -