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  • Title: Effects of thalidomide on Th17, Treg cells and TGF-β1/Smad3 pathway in a mouse model of systemic sclerosis.
    Author: Lu Y, Zhao C, Lei L, Tao Z, Zheng L, Wen J, Li X.
    Journal: Int J Rheum Dis; 2020 Mar; 23(3):406-419. PubMed ID: 31840939.
    Abstract:
    OBJECTIVE: To evaluate the immune regulatory and anti-fibrosis function of thalidomide (Thal) in systemic sclerosis (SSc), we investigated the effects of Thal on: (a) Th17 and Treg cell production; (b) related factors expression; and (c) transforming growth factor (TGF)-β1/Smad3 pathway, using a mouse model of SSc. METHODS: Forty female BALB/c mice were randomly divided into a normal control (NC) group, SSc group (bleomycin [BLM]-induced experimental SSc), BLM + Thal (10 mg/kg/day) group, BLM + Thal (20) group, and BLM + Thal (30) group. Thal was administered a day after BLM. At the end of the animal experiments, mouse tissues were collected for detection of pathological changes and hydroxyproline content. Flow cytometry, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, Western blot and other methods were used to measure Th17, Treg cell population and their related factors, as well as TGF-β1/Smad3 pathway expression. RESULTS: Thal treatment: (a) reduced skin, and pulmonary tissue fibrosis, inflammation score, and hydroxyproline content (P < .001) in BLM-induced SSc mice; (b) reduced the percentages of Th17 cells and associated interleukin (IL)-17A expression (both P < .05) but increased the percentages of Treg cells and its transcription factor Foxp3 expression (both P < .05); (c) correlation analysis found positive correlations between Th17/Treg ratio, the inflammatory score of the skin and pulmonary tissues, hydroxyproline content, and type I collagen messenger RNA expression (r = .8546, .8656, .6902, .6807, .8118, and .8424, respectively, P < .01); (d) Thal inhibited TGF-β1 expression and Smad3 phosphorylation (both P < .05); (e) TGF-β1 was positively correlated with the IL-17A and Th17/Treg ratio (r = .5856, P = .005; r = .6684, P = .0107, respectively). CONCLUSION: Thal can effectively prevent skin and pulmonary tissue fibrosis in a mouse model of SSc through the TGF-β1/Smad3 signaling pathway and can rectify the distortion of the Th17/Treg balance in SSc by potentially regulating Th17 and Treg cell production, as well as their related factors expression.
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