Genome-wide association studies (GWAS) have revealed numerous MS-risk alleles in the IL-6/STAT3, IL-12/STAT4, and IL-23/STAT3-pathways implicated in the differentiation of Th1 and Th17 cells.
In conclusion, let-7f-5p functions as a potential inhibitor of Th17 differentiation in the pathogenesis of MS by targeting STAT3 and may serve as a new therapeutic target.
A comprehensive MS-specific miRNA-TF co-regulatory network was hypothesized; among others, SP1, RELA, NF-κB, TP53, AR, MYC, HDAC1, and STAT3 regulated the transcription of 61 targets.
Gas6 stimulation also resulted in activation of STAT3 in optic nerves as well as downregulation of multiple genes involved in MS development, including matrix metalloproteinase-9 (MMP9), which may decrease the integrity of the blood-brain barrier and is found upregulated in MS lesions.
The protective haplotype for MS in STAT3 is a risk allele for Crohn disease, implying that STAT3 represents a shared risk locus for at least two autoimmune diseases.
Polymorphisms in the STAT3 region (rs3809758/rs744166/rs1026916/rs12948909) were genotyped and the inferred haplotypes were subsequently analyzed in 860 IBD and 1540 MS Spanish patients and 1720 ethnically matched controls.
These findings indicated that curcumin amelioration EAE was, to a large extent, due to inhibit differentiation and development of Th17 cells depends on down-regulating expression of IL-6, IL-21, RORgammat signaling and inhibition STAT3-phosphorylation, suggests it is useful in the treatment of MS and other Th17 cell-mediated inflammatory diseases.
Several observations suggest that the interferon system may be of interest in the study of MS development To investigate whether polymorphism in components of the IFN system and the JAK-STAT pathway influence susceptibility to MS, we performed a linkage analysis between polymorphic loci in or close to the IFN gamma, IFN gamma receptor, IFN alpha/beta receptor, JAK 1, STAT 1 and STAT 3 genes in 27 Swedish families with at least two members having MS. Tests for transmission disequilibrium and nonparametric linkage analysis gave negative results.