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 -