Constitutive STAT3 Activation in Intestinal T Cells from Patients with Crohn's Disease

• Published in: The Journal of biological chemistry 2003-05, Vol.278 (19), p.16777-16781
• Main Authors: Lovato, Paola, Brender, Christine, Agnholt, Jørgen, Kelsen, Jens, Kaltoft, Keld, Svejgaard, Arne, Eriksen, Karsten Wessel, Woetmann, Anders, Ødum, Niels
• Format: Article
• Language: English
• Subjects: Adult; Crohn Disease - immunology; Crohn Disease - metabolism; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; Humans; Immunity, Mucosal; Intestinal Mucosa - metabolism; Middle Aged; Repressor Proteins - metabolism; Signal Transduction; STAT3 Transcription Factor; STAT4 Transcription Factor; T-Lymphocytes - metabolism; Trans-Activators - immunology; Trans-Activators - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M207999200

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.