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BACKGROUND miR-155-5p is associated with autoimmune diseases. T helper 17 (Th17) cells, interleukin (IL)-17, and suppressor of cytokines signaling 1 (SOCS1) have important roles in the pathogenesis of systemic sclerosis (SSc). The purpose of this study was to explore the role of miR-155-5p in the regulation of IL-17 and SOCS1 expression in Th17 cells and the subsequent effect on SSc disease progression. METHODS Th17 cells were isolated from peripheral blood mononuclear cells of SSc patients and healthy controls (HCs). RT-qPCR and western blotting were used to examine the expression patterns of miR-155-5p, IL-17, and SOCS1. Luciferase reporter assays were performed to confirm SOCS1 as a target of miR-155-5p. RNA pull-down assays were performed to detect the interaction of IL-17 and SOCS1 with miR-155-5p. In situ hybridization was performed to analyze the co-expression pattern of miR-155-5p and IL17A in Th17 cells. RESULTS The levels of Th17 cell-derived miR-155-5p were significantly up-regulated in SSc patients compared with HCs, and its levels were negatively correlated with SOCS1 levels. Meanwhile, miR-155-5p positively regulated IL-17 expression levels in Th17 cells isolated from SSc patients as the disease progressed. Using pmirGLO vectors, SOCS1 was confirmed as a target of miR-155-5p. The binding status of IL-17 and SOCS1 to miR-155-5p was related to SSc progression. An increase in the co-localization of miR-155-5p and IL-17 was associated with greater SSc progression. CONCLUSIONS IL-17 and SOCS1 expression modulated by Th17 cell-derived miR-155-5p are critical for SSc progression, which may provide novel insights into the pathogenesis of SSc.

Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human na{\{i}}ve and memory CD4 T cells here we show that both adrenergic- and glucocorticoid-mediated stress signalling pathways play a CD4 na{\"{i}}ve T-cell-intrinsic role in regulating the Th1/Th2 differentiation balance. Both stress hormones reduced the Th1 programme and cytokine production by inhibiting mTORC1 signalling via two parallel mechanisms. Stress hormone signalling inhibited mTORC1 in na{\"{i}}ve CD4 T cells (1) by affecting the PI3K/AKT pathway and (2) by regulating the expression of the circadian rhythm gene period circadian regulator 1 (PER1). Both stress hormones induced the expression of PER1 which inhibited mTORC1 signalling thus reducing Th1 differentiation. This previously unrecognized cell-autonomous mechanism connects stress hormone signalling with CD4 T-cell differentiation via mTORC1 and a specific circadian clock gene namely PER1."