Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease

Paola Lovato; Christine Brender; Jørgen Agnholt; Jens Kelsen; Keld Kaltoft; Arne Svejgaard; Karsten Wessel Eriksen; Anders Woetmann; Niels Ødum

doi:10.1074/jbc.M207999200

Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease

Paola Lovato, Christine Brender, Jørgen Agnholt, Jens Kelsen, Keld Kaltoft, Arne Svejgaard, Karsten Wessel Eriksen, Anders Woetmann, Niels Ødum

147 Citations (Scopus)

Abstract

Via cytoplasmic signal transduction pathways, cytokines induce a variety of biological responses and modulate the outcome of inflammatory diseases and malignancies. Crohn's disease is a chronic inflammatory bowel disease of unknown etiology. Perturbation of the intestinal cytokine homeostasis is believed to play a pivotal role, but the pathogenesis of Crohn's disease is not fully understood. Here, we study intestinal T cells from Crohn's disease and healthy volunteers. We show that STAT3 and STAT4 are constitutively activated in Crohn's patients but not in healthy volunteers. The activation is specific, because other STAT proteins are not constitutively activated. Furthermore, the STAT3 regulated protein, SOCS3, is also constitutively expressed in Crohn's patients but not in healthy volunteers. Taken together, these data provide evidence of abnormal STAT/SOCS signaling in Crohn's disease. This aberrant activation, so far noted only in malignant cells, establish a new critical approach for better understanding the immunopathogenesis of Crohn's disease.

Original language	English
Journal	Journal of Biological Chemistry
Volume	278
Issue number	19
Pages (from-to)	16777-81
Number of pages	4
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.M207999200
Publication status	Published - 2003

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10.1074/jbc.M207999200

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@article{38d9eea0fcf011ddb219000ea68e967b,

title = "Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease",

abstract = "Via cytoplasmic signal transduction pathways, cytokines induce a variety of biological responses and modulate the outcome of inflammatory diseases and malignancies. Crohn's disease is a chronic inflammatory bowel disease of unknown etiology. Perturbation of the intestinal cytokine homeostasis is believed to play a pivotal role, but the pathogenesis of Crohn's disease is not fully understood. Here, we study intestinal T cells from Crohn's disease and healthy volunteers. We show that STAT3 and STAT4 are constitutively activated in Crohn's patients but not in healthy volunteers. The activation is specific, because other STAT proteins are not constitutively activated. Furthermore, the STAT3 regulated protein, SOCS3, is also constitutively expressed in Crohn's patients but not in healthy volunteers. Taken together, these data provide evidence of abnormal STAT/SOCS signaling in Crohn's disease. This aberrant activation, so far noted only in malignant cells, establish a new critical approach for better understanding the immunopathogenesis of Crohn's disease.",

author = "Paola Lovato and Christine Brender and J{\o}rgen Agnholt and Jens Kelsen and Keld Kaltoft and Arne Svejgaard and Eriksen, {Karsten Wessel} and Anders Woetmann and Niels {\O}dum",

note = "Keywords: Adult; Crohn Disease; DNA-Binding Proteins; Humans; Immunity, Mucosal; Intestinal Mucosa; Middle Aged; Repressor Proteins; STAT3 Transcription Factor; STAT4 Transcription Factor; Signal Transduction; T-Lymphocytes; Trans-Activators",

year = "2003",

doi = "10.1074/jbc.M207999200",

language = "English",

volume = "278",

pages = "16777--81",

journal = "Journal of Biological Chemistry",

issn = "0021-9258",

publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

number = "19",

}

TY - JOUR

T1 - Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease

AU - Lovato, Paola

AU - Brender, Christine

AU - Agnholt, Jørgen

AU - Kelsen, Jens

AU - Kaltoft, Keld

AU - Svejgaard, Arne

AU - Eriksen, Karsten Wessel

AU - Woetmann, Anders

AU - Ødum, Niels

N1 - Keywords: Adult; Crohn Disease; DNA-Binding Proteins; Humans; Immunity, Mucosal; Intestinal Mucosa; Middle Aged; Repressor Proteins; STAT3 Transcription Factor; STAT4 Transcription Factor; Signal Transduction; T-Lymphocytes; Trans-Activators

PY - 2003

Y1 - 2003

N2 - Via cytoplasmic signal transduction pathways, cytokines induce a variety of biological responses and modulate the outcome of inflammatory diseases and malignancies. Crohn's disease is a chronic inflammatory bowel disease of unknown etiology. Perturbation of the intestinal cytokine homeostasis is believed to play a pivotal role, but the pathogenesis of Crohn's disease is not fully understood. Here, we study intestinal T cells from Crohn's disease and healthy volunteers. We show that STAT3 and STAT4 are constitutively activated in Crohn's patients but not in healthy volunteers. The activation is specific, because other STAT proteins are not constitutively activated. Furthermore, the STAT3 regulated protein, SOCS3, is also constitutively expressed in Crohn's patients but not in healthy volunteers. Taken together, these data provide evidence of abnormal STAT/SOCS signaling in Crohn's disease. This aberrant activation, so far noted only in malignant cells, establish a new critical approach for better understanding the immunopathogenesis of Crohn's disease.

AB - Via cytoplasmic signal transduction pathways, cytokines induce a variety of biological responses and modulate the outcome of inflammatory diseases and malignancies. Crohn's disease is a chronic inflammatory bowel disease of unknown etiology. Perturbation of the intestinal cytokine homeostasis is believed to play a pivotal role, but the pathogenesis of Crohn's disease is not fully understood. Here, we study intestinal T cells from Crohn's disease and healthy volunteers. We show that STAT3 and STAT4 are constitutively activated in Crohn's patients but not in healthy volunteers. The activation is specific, because other STAT proteins are not constitutively activated. Furthermore, the STAT3 regulated protein, SOCS3, is also constitutively expressed in Crohn's patients but not in healthy volunteers. Taken together, these data provide evidence of abnormal STAT/SOCS signaling in Crohn's disease. This aberrant activation, so far noted only in malignant cells, establish a new critical approach for better understanding the immunopathogenesis of Crohn's disease.

U2 - 10.1074/jbc.M207999200

DO - 10.1074/jbc.M207999200

M3 - Journal article

C2 - 12615922

SN - 0021-9258

VL - 278

SP - 16777

EP - 16781

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 19

ER -

Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease

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