We observed a unique phospho-STAT3(S727) response in patients with Montreal B2 Crohn's disease, particularly in response to IL-6 leading to increased TGF-β1, collagen, and CTGF production in ileal strictures.
Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994.
We recruited 369 AJ CD patients and 503 AJ controls, genotyped 22 single nucleotide polymorphisms (SNPs) at or near 10 CD-associated genes, NOD2, IL23R, IRGM, ATG16L1, PTGER4, NKX2-3, IL12B, PTPN2, TNFSF15 and STAT3, and assessed their association with CD status.
Other than genetic variants of IL-10 receptors, IL-10 and STAT3 genes are also associated with IBD, emphasizing the involvement of the IL-10 signalling cascade in the pathogenesis of CD and UC.
<i>STAT3</i> Genotypic Variant <i>rs744166</i> and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn's Disease.
In addition, IL-10-mediated suppression of TNFα production upon LPS stimulation and IL-10-induced STAT3 phosphorylation were attenuated in patients with CD versus controls.
Elevated plasma IL-6 levels were detected in CD (P = 0.004), which strongly correlated with disease activity (ρ = 0.690, P<0.001) but not with IL-6-induced STAT3 phosphorylation.
In addition, triptolide (20ng/ml) in vitro was able to down-regulate the IL-6/STAT3 pathway and reduce IL-17 expression in cultured colonic explants from patients with Crohn's disease (CD).
Of CD susceptibility genes identified by genome-wide association scan IL-23A, JAK2, and STAT3 were upregulated in the CD group, confirming the dysregulation of Th17 signaling.