Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn’s disease

Figure 1 The JAK/STAT pathway. A: Canonical Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-signaling initiates with the association of cytokines and their corresponding transmembrane receptors; B: Cytokine binding brings JAKs in proximity to the receptor, leading to phosphorylation of both the JAKs themselves and the cytoplasmic tails of the receptors, thereby creating docking sites for STAT monomers; C: STAT tyrosine phosphorylation (p-Tyr) is the major activating event, leading to dimerization of STATs, translocation to the nucleus, DNA binding of STAT dimers and subsequent target gene induction. JAK: Janus kinase; STAT: Signal transducer and activator of transcription.

Figure 2 Differentially regulated STATs in T-cells from patients with inflammatory bowel disease. In T-cells, signal transducer and activator of transcription (STAT)1 signaling is increased in Crohn`s disease (CD) but not ulcerative colitis (UC), while STAT3 is associated with a critical role in both UC and CD pathogenesis and overactivation is linked to increased intestinal inflammation. There is stronger evidence of STAT4 signaling in CD but STAT4 induction is also apparent in UC, while the STAT6 pathway seems to be more affected in UC. Down-regulation of STAT5 in CD leads to inhibition of regulatory T-cells. Strength of arrows indicates available supporting data. CD: Crohn’s disease; IFN: Interferon; IFNγ-R: Interferon γ receptor; IL: Interleukin; IL4R: Interleukin 4 receptor; IL12R: Interleukin 12 receptor; STAT: Signal transducer and activator of transcription; Th: T-helper cell; Treg: Regulatory T-cell; UC: Ulcerative colitis.

Figure 3 Differentially regulated STATs in monocytes and monocyte-derived cells from patients with inflammatory bowel disease. Signal transducer and activator of transcription (STAT)1 activation seems to be different in myeloid cells of patients with Crohn’s disease (CD) and ulcerative colitis (UC). Although induced in CD, STAT1 is greatly elevated in monocytes and monocyte-derived cells from UC. There is evidence for increased STAT3 signaling in CD, while UC was not investigated. For STAT2, STAT4, STAT5, and STAT6 there are no solid data available from patients with IBD. Count of arrows indicates strength of increase in a direct comparison of UC and CD. CD: Crohn’s disease; IFN: Interferon; IFNAR: Interferon α receptor; IFNγ-R: Interferon γ receptor; IL: Interleukin; IL10R: Interleukin 10 receptor; STAT: Signal transducer and activator of transcription; UC: Ulcerative colitis.