Increased sensitivity to interferon-alpha in psoriatic T cells

Karsten Wessel Eriksen; Paola Lovato; Lone Skov; Thorbjørn Krejsgaard; Keld Kaltoft; Carsten Geisler; Niels Ødum

doi:10.1111/j.0022-202X.2005.23864.x

Increased sensitivity to interferon-alpha in psoriatic T cells

Karsten Wessel Eriksen, Paola Lovato, Lone Skov, Thorbjørn Krejsgaard, Keld Kaltoft, Carsten Geisler, Niels Ødum

Cellebiologi og Fysiologi

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

79 Citationer (Scopus)

Abstract

Udgivelsesdato: 2005-Nov

Originalsprog	Engelsk
Tidsskrift	Journal of Investigative Dermatology
Vol/bind	125
Udgave nummer	5
Sider (fra-til)	936-44
Antal sider	8
ISSN	0022-202X
DOI	https://doi.org/10.1111/j.0022-202X.2005.23864.x
Status	Udgivet - 2005

Bibliografisk note

Keywords: Apoptosis; Humans; Interferon Type II; Interferon-alpha; Promoter Regions (Genetics); Psoriasis; STAT4 Transcription Factor; Signal Transduction; T-Lymphocytes

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10.1111/j.0022-202X.2005.23864.x

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Citationsformater

@article{acfddd70b09f11ddb538000ea68e967b,

title = "Increased sensitivity to interferon-alpha in psoriatic T cells",

abstract = "Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important role in host defense against infections, but recent data have also implicated IFN-alpha in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling spontaneously develop a psoriasis-like inflammatory skin disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-alpha signaling leads to an increased binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell growth. In contrast, to STAT responses to other cytokines were not changed in psoriasis. In conclusion, we provide evidence that psoriatic T cells have an increased sensitivity to IFN-alpha. Thus, our data suggest that increased IFN-alpha signaling is involved in the pathogenesis of psoriasis.",

author = "Eriksen, {Karsten Wessel} and Paola Lovato and Lone Skov and Thorbj{\o}rn Krejsgaard and Keld Kaltoft and Carsten Geisler and Niels {\O}dum",

note = "Keywords: Apoptosis; Humans; Interferon Type II; Interferon-alpha; Promoter Regions (Genetics); Psoriasis; STAT4 Transcription Factor; Signal Transduction; T-Lymphocytes",

year = "2005",

doi = "10.1111/j.0022-202X.2005.23864.x",

language = "English",

volume = "125",

pages = "936--44",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "nature publishing group",

number = "5",

}

TY - JOUR

T1 - Increased sensitivity to interferon-alpha in psoriatic T cells

AU - Eriksen, Karsten Wessel

AU - Lovato, Paola

AU - Skov, Lone

AU - Krejsgaard, Thorbjørn

AU - Kaltoft, Keld

AU - Geisler, Carsten

AU - Ødum, Niels

N1 - Keywords: Apoptosis; Humans; Interferon Type II; Interferon-alpha; Promoter Regions (Genetics); Psoriasis; STAT4 Transcription Factor; Signal Transduction; T-Lymphocytes

PY - 2005

Y1 - 2005

N2 - Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important role in host defense against infections, but recent data have also implicated IFN-alpha in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling spontaneously develop a psoriasis-like inflammatory skin disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-alpha signaling leads to an increased binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell growth. In contrast, to STAT responses to other cytokines were not changed in psoriasis. In conclusion, we provide evidence that psoriatic T cells have an increased sensitivity to IFN-alpha. Thus, our data suggest that increased IFN-alpha signaling is involved in the pathogenesis of psoriasis.

AB - Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important role in host defense against infections, but recent data have also implicated IFN-alpha in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling spontaneously develop a psoriasis-like inflammatory skin disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-alpha signaling leads to an increased binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell growth. In contrast, to STAT responses to other cytokines were not changed in psoriasis. In conclusion, we provide evidence that psoriatic T cells have an increased sensitivity to IFN-alpha. Thus, our data suggest that increased IFN-alpha signaling is involved in the pathogenesis of psoriasis.

U2 - 10.1111/j.0022-202X.2005.23864.x

DO - 10.1111/j.0022-202X.2005.23864.x

M3 - Journal article

C2 - 16297193

SN - 0022-202X

VL - 125

SP - 936

EP - 944

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 5

ER -