Regulation of Suppressors of Cytokine Signaling as a Therapeutic Approach in Autoimmune Diseases, with an Emphasis on Multiple Sclerosis

Figure 1

IFNβ and simvastatin induce expression of SOCS1 and SOCS3. IFNβ induces the phosphorylation of STAT1 and STAT3. STAT3 phosphorylation leads to the induction of SOCS3 expression, which downregulates the expression of IL-23 and IL-1β. The cytokines IL-23 and IL-1β promote the development of Th17-cells. In B-cells, the induction of STAT1 results in the expression of SOCS1, which downregulates the costimulatory molecule CD40. IFNβ also acts on naïve CD45RA by inducing STAT1 phosphorylation, which subsequently induces SOCS3 that suppresses the STAT3 activation responsible for RORc gene transcription. Simvastatin induces the phosphorylation of STAT3 in APCs that leads to the expression of SOCS3, which in turn inhibits the gene transcription of IL-1β and IL-23.