Finally, activated STAT3 elicited the expression of interleukin-6 (IL-6), thereby contributing to RABV-associated encephalomyelitis; however, PGG restored the level of IL-6 <i>in vitro</i> and <i>in vivo</i> in a SOCS3/STAT3-dependent manner.
Collectively, our findings highlight that miR-409-3p and miR-1896 co-ordinately promote the production of inflammatory cytokines in reactive astrocytes through the SOCS3/STAT3 pathway and enhance reactive astrocyte-directed chemotaxis of CD4<sup>+</sup> T cells, leading to aggravate pathogenesis in EAE mice.
Thus, our studies delineate a mechanism connecting signaling related polyubiquitination of Malt1 and Stat3, leading to NF-kB activation and RORγt expression, to pathogenic Th17 cell function in EAE.
Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis.
Depletion of Ly6G<sup>+</sup> cells or dysfunction of Ly6G<sup>+</sup> cells through conditional ablation of STAT3 led to the selective accumulation of GM-CSF-producing B cells in the CNS compartment, which in turn promoted an activated microglial phenotype and lack of recovery from EAE.
Importantly, the IL-12p35-mediated expansion of Treg and Breg cells and its amelioration of EAE correlated with inhibition of cytokine-induced activation of STAT1/STAT3 pathways.
Together, our data demonstrated that SH479 ameliorated EAE by regulating the T<sub>H</sub>17/Treg balance through inhibiting the STAT3 and NF-<i>κ</i>B pathways while activating the STAT5 pathway, suggesting that SH479 is a potential novel drug candidate for autoimmune diseases including MS.
By measuring the downstream markers phospho-mTOR (p-mTOR)/mTOR and phospho-signal transducer and activator of transcription 3 (p-STAT3)/STAT3, we showed that rapamycin suppressed the mTOR-STAT3 pathway in EAE mice.
In addition to the in vitro inhibition of human Th17 cells in a dose-dependent manner, the antagonizing effect of hIL23R-CHR was confirmed by reduced levels of IL-23 in both blood and brain of EAE mice and STAT3 phosphorylation in vivo.
Mice with targeted deletion of STAT3 in CD4(+) T-cells do not develop experimental autoimmune uveitis (EAU) or experimental autoimmune encephalomyelitis (EAE), in part, because they cannot generate pathogenic Th17 cells.