Deficient SOCS3 and SHP-1 Expression in Psoriatic T Cells

TY - JOUR

T1 - Deficient SOCS3 and SHP-1 Expression in Psoriatic T Cells

AU - Eriksen, Karsten W

AU - Woetmann, Anders

AU - Skov, Lone

AU - Krejsgaard, Thorbjørn

AU - Bovin, Lone F

AU - Hansen, Mikkel L

AU - Grønbæk, Kirsten

AU - Billestrup, Nils

AU - Nissen, Mogens H

AU - Geisler, Carsten

AU - Wasik, Mariusz A

AU - Odum, Niels

PY - 2010/6

Y1 - 2010/6

N2 - IFN-α 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-α, but the pathological mechanisms behind the hyperresponsiveness to IFN-α 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-α 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-α-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-α response. Similarly, forced expression of SOCS3 and SHP-1 inhibits IFN-α 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-α.

AB - IFN-α 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-α, but the pathological mechanisms behind the hyperresponsiveness to IFN-α 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-α 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-α-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-α response. Similarly, forced expression of SOCS3 and SHP-1 inhibits IFN-α 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-α.

U2 - 10.1038/jid.2010.6

DO - 10.1038/jid.2010.6

M3 - Journal article

C2 - 20130595

SN - 0022-202X

VL - 130

SP - 1590

EP - 1597

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 6

ER -