Deficient SOCS3 and SHP-1 Expression in Psoriatic T Cells

Karsten W. Eriksen, Anders Woetmann, Lone Skov, Thorbjørn Krejsgaard, Lone F. Bovin, Mikkel L. Hansen, Kirsten Grønbæk, Nils Billestrup, Mogens H. Nissen, Carsten Geisler, Mariusz A. Wasik, Niels Ødum
2010 Journal of Investigative Dermatology  
a 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-a, but the pathological mechanisms behind the hyperresponsiveness to IFN-a 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-a and a low baseline expression of the SH2-domain-containing protein-tyrosine phosphatase
more » ... yrosine phosphatase (SHP)-1 when compared with skin T cells from nonpsoriatic donors. Moreover, IFN-a-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-a response. Similarly, forced expression of SOCS3 and SHP-1 inhibits IFN-a 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-a.
doi:10.1038/jid.2010.6 pmid:20130595 fatcat:z6ffbtsggje7jk2e75hz25wzcy