The Role of Signal Transducers and Activators of Transcription in T Inflammatory Bowel Diseases

Signal transducers and activators of transcription (STAT) proteins are intracellular effector molecules of cytokine-modulated signaling. On the one hand, they play an important role in hematopoiesis and the development of the human immune system. STAT transcription factors are necessary for embryogenesis and the maintenance of the mammalian immune response. In the adult, STAT signaling is responsible for T-cell polarization toward interferon γ–secreting Th1 T cells or interleukin 4–producing Th2 cells. On the other hand, these proteins are involved in the regulation of T-cell survival. STAT activation is strongly associated with tyrosine phosphorylation by tyrosine kinases, namely Jak1, Jak2, Jak3, and Tyk2. Counterregulatory mechanisms protecting from overwhelming STAT activation are represented by protein inhibitors of activated STATs and the SOCS family proteins. Because STAT proteins are key response elements of cytokine-induced T-cell activation, the characterization of STAT proteins is one step to elucidate disturbed T-cell function in inflammatory bowel disease. In particular, an activation of STAT-4 and STAT-3 in T cells seems to play a key pathogenic role in Crohn's disease.