Effects of thalidomide on Th17, Treg cells and TGF‐β1/Smad3 pathway in a mouse model of systemic sclerosis

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.