期刊
JOURNAL OF INVESTIGATIVE DERMATOLOGY
卷 130, 期 6, 页码 1590-1597出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2010.6
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资金
- University of Copenhagen
- Danish Medical Research Council
- Copenhagen Cluster of Immunology
- Novo Nordic Foundation
- Lundbeck Foundation
- Danish National Advanced Technology Foundation
- Neye foundation
- Danish Medical Association Research Foundation
- Danish Cancer Research Foundation
- Danish Cancer Society
- Carlsberg Foundation
- AP Moller Foundation for the Advancement of Medical Science
- US National Cancer Institute
IFN-alpha and skin-infiltrating activated T lymphocytes have important roles in the pathogenesis of psoriasis. T cells from psoriatic patients display an increased sensitivity to IFN-alpha, but the pathological mechanisms behind the hyperresponsiveness to IFN-alpha remained unknown. In this study, we show that psoriatic T cells display deficient expression of the suppressor of cytokine signaling (SOCS) 3 in response to IFN-alpha and a low baseline expression of the SH2-domain-containing protein-tyrosine phosphatase (SHP)-1 when compared with skin T cells from nonpsoriatic donors. Moreover, IFN-alpha-stimulated psoriatic T cells show enhanced activation of JAKs (JAK1 and TYK2) and signal transducers and activators of transcription. Increased expression of SOCS3 proteins resulting from proteasomal blockade partially inhibits IFN-alpha response. Similarly, forced expression of SOCS3 and SHP-1 inhibits IFN-alpha signaling in psoriatic T cells. In conclusion, our data suggest that loss of regulatory control is involved in the aberrant hypersensitivity of psoriatic T cells to IFN-alpha.
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