Collectively, the results suggest that <i>STAT3</i> in T cells may be a therapeutic target in ulcerative colitis by balancing the immune response through T cell homeostasis.
Altogether, IL-9 participates in the pathogenesis of UC through STAT3/SOCS3 signaling pathway and has the potential to serve as a possible therapeutic candidate in patients with UC.
Ulcerative colitis (UC) is characterized by aberrant regulation of tight junctions (TJ), signal transducer and activator of transcription 3 (STAT3), and interleukin (IL)-8/18, which lead to intestinal barrier defects.
Interleukin‑6 (IL‑6)/signal transducer and activator of transcription 3 (STAT3) pathway plays essential roles in the development of inflammatory diseases including ulcerative colitis (UC).
Our study provides evidence that miR-495 improves the intestinal mucosal barrier function by targeting STAT3 through inhibiting the JAK/STAT3 signaling pathway in UC mice.
This is the first study of the single marker association of IL23R, JAK2, and STAT3 polymorphisms with ulcerative colitis and Crohn's disease in a Turkish population.
We investigated whether high SOCS3 increased risk for relapse through violating STAT3-dependent protective effects of interleukin (IL)-22 during UC remission.
Our study implies that the STAT3rs2293152 polymorphism may be associated with the occurrence of UC and might be used as a predictive factor for UC in the Chinese Han population.
The results indicated that the STAT3rs744166 polymorphism was associated with CD and UC susceptibility (CD: GA+AA vs. GG, OR = 1.20, 95%CI, 1.11-1.30, I2 = 0%, Punadjusted<0.00001, PBonferroni<0.00005, PFDR<0.00001; UC: GA+AA vs. GG, OR = 1.21, 95%CI, 1.08-1.36, I2 = 1%, Punadjusted = 0.001, PBonferroni = 0.005, PFDR = 0.00125).
Levels of miR-124 were decreased, whereas levels of STAT3 phosphorylation increased in colon tissues from pediatric patients with active UC compared with those with inactive disease.
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.
Our data confirm the association between JAK2 rs10758669 (p = 0.026, OR = 1.25, 95% CI = 1.04-1.50) and STAT3rs744166 (p = 0.04, OR = 0.83, 95% CI = 0.688-0.998) with CD, but not UC.
Data on genetic interaction reveals that the above JAK2 and STAT3 risk alleles contribute to CD susceptibility in combination with each other (OR: 2.218; 95% CI: 1.097-4.487; P = 0.024), while the JAK2 variant shows a tendency to confer UC risk only on a wild-type STAT3 background (OR: 1.997, 95%CI: 0.994-4.009, P = 0.049).
Inhibition of ulcerative colitis in mice after oral administration of a polyphenol-enriched cocoa extract is mediated by the inhibition of STAT1 and STAT3 phosphorylation in colon cells.
The originally described association of IBD with STAT3 polymorphisms is corroborated for the two clinical phenotypes, CD and UC, in an independent population.
In conclusion, the IL-10R1 S138G variant is a loss-of-function allele for IL-10-induced STAT1 and STAT3 activation but does not protect from UC susceptibility.