Cytokine Signalling Forum

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STA-21, a promising STAT3 inhibitor that reciprocally regulates Th17 and Treg, inhibits osteoclastgenesis and alleviates autoimmune inflammation

Park JS, Kwok SK, Lim MA et al. - Arthritis and Rheumatism doi: 10.1002/art.38305

STAT3 (signal transducer and activator of transcription 3) is the major transcription factor in the differentiation of Th17 cells, which along with IL-17 are significant in the development of RA. STA-21 is a new small molecule with significant inhibitory effects on STAT3, impeding DNA binding activity, dimerization and STAT3-dependent luciferase activity. While the effect of STA-21 in RA has not been fully determined, it has been hypothesised that STA-21 will suppress arthritis in animal models of RA. Park et al. used several measures, including in vivo testing in IL-1 receptor antagonist deficient mice, to show the therapeutic effect. The effects included the decreased activity of Th17 cells and increased Foxp3-expressing Treg cells. The effects on osteoclasts were also measured and an adoptive transfer of CD4+CD25+ T cells was performed to verify the Treg cells produced by STA-21 would work in vivo. The results obtained suggest that STA-21 presents a potential therapeutic option for RA.