Deficient SOCS3 and SHP-1 Expression in Psoriatic T Cells
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Deficient SOCS3 and SHP-1 Expression in Psoriatic T Cells. / Eriksen, Karsten W; Woetmann, Anders; Skov, Lone; Krejsgaard, Thorbjørn; Bovin, Lone F; Hansen, Mikkel L; Grønbæk, Kirsten; Billestrup, Nils; Nissen, Mogens H; Geisler, Carsten; Wasik, Mariusz A; Odum, Niels.
In: Journal of Investigative Dermatology, Vol. 130, No. 6, 2010, p. 1590-7.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2010
N2 - 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.Journal of Investigative Dermatology advance online publication, 4 February 2010; doi:10.1038/jid.2010.6.
AB - 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.Journal of Investigative Dermatology advance online publication, 4 February 2010; doi:10.1038/jid.2010.6.
U2 - 10.1038/jid.2010.6
DO - 10.1038/jid.2010.6
M3 - Journal article
C2 - 20130595
VL - 130
SP - 1590
EP - 1597
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 6
ER -
ID: 18051087