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• W3023699186 endingPage "3069" @default.
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• W3023699186 abstract "Abstract Objectives To elucidate the molecular mechanisms underlying pathogenic Th17 cells, we investigated the modulation of epigenetic modifications and its association with SLE. Methods Naive CD4+ T cells were cultured in Th17 polarizing conditions for 5 days and then treated with various cytokines, including IL-23. Expression of Th17 cell–related markers and phosphorylation of signal transducers and activators of transcription (pSTATs) were analysed using flow cytometry and quantitative PCR. Histone modifications were assessed using chromatin immunoprecipitation PCR. T cell phenotypes and pSTATs were analysed in blood samples of patients with SLE (n = 28). Finally, the effects of baricitinib on memory Th17 cells were investigated in SLE patients (n = 12). Results Stimulation of resting Th17 cells with IL-23 promoted maturation of these cells (P &lt; 0.0001). IL-23 induced pSTAT3, but not pSTAT4, during Th17 cell maturation (P &lt; 0.05). IL-23-induced STAT3 directly bound the RORγT gene locus. This was accompanied by induction of the H3H4me3 permissive mark and reduction of the H3K27me3 repressive mark, leading to enhanced RORγT gene expression. IL-23-induced expansion of Th17 cells and pSTAT3 were suppressed by the addition of baricitinib in a concentration-dependent manner (P &lt; 0.05). In memory Th17 cells from SLE patients, pSTAT3 was hypersensitized by IL-23 stimulation and inhibited by baricitinib (P &lt; 0.05). Conclusion The results of this study indicate that IL-23/STAT3 signalling plays a fundamental role in Th17 cell maturation through transcriptional and epigenetic modifications in patients with SLE. This mechanism may underlie pathogenic Th17 cell expansion and may lead to identification of novel therapeutic targets for SLE." @default.
• W3023699186 created "2020-05-13" @default.
• W3023699186 creator A5015953107 @default.
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• W3023699186 date "2020-05-06" @default.
• W3023699186 modified "2023-10-01" @default.
• W3023699186 title "Interleukin-23 drives expansion of Thelper 17 cells through epigenetic regulation by signal transducer and activators of transcription 3 in lupus patients" @default.
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• W3023699186 doi "https://doi.org/10.1093/rheumatology/keaa176" @default.
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• W3023699186 hasPublicationYear "2020" @default.
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