Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease.
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.
Lovato
Paola
P
Institute of Medical Microbiology and Immunology, the Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark.
Brender
Christine
C
Agnholt
Jørgen
J
Kelsen
Jens
J
Kaltoft
Keld
K
Svejgaard
Arne
A
Eriksen
Karsten Wessel
KW
Woetmann
Anders
A
Ødum
Niels
N
D000328:Adult; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000378:metabolism*; D008875:Middle Aged; D012097:Repressor Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators