Deficient SOCS3 and SHP-1 expression in psoriatic T cells.
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.
Eriksen
Karsten W
KW
Department of International Health, Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3c,Copenhagen, Denmark. keriksen@sund.ku.dk
Woetmann
Anders
A
Skov
Lone
L
Krejsgaard
Thorbjørn
T
Bovin
Lone F
LF
Hansen
Mikkel L
ML
Grønbaek
Kirsten
K
Billestrup
Nils
N
Nissen
Mogens H
MH
Geisler
Carsten
C
Wasik
Mariusz A
MA
Ødum
Niels
N
D016022:Case-Control Studies; D002460:Cell Line; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000172:deficiency*; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
D016898:Interferon-alpha; C106644:SOCS3 protein, human; D050791:STAT Transcription Factors; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053612:Janus Kinases; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6