Blocking sphingosine 1-phosphate receptor 1 with modulators reduces immune cells infiltration and alleviates endometriosis in mice

Abstract

Research questionDo sphingosine 1-phosphate (S1P) modulators have therapeutic effects on endometriosis in mice and, if they do, which receptor is responsible for these effects? DesignA surgically induced endometriosis mouse model was established. In the pilot experiment, lesions were harvested to assess fibrosis and inflammation and determine the optimal concentration of a broad-spectrum S1P modulator, FTY720. Subsequently, FTY720 was compared with a selective S1P receptor 1 modulator, SEW2871 to evaluate their effects on endometriotic lesion growth, fibrosis, inflammation and immune cell infiltration. ResultsThe results demonstrated that both FTY720 and SEW2871, two S1P receptor modulators, effectively inhibited the growth and fibrosis of endometriotic lesions. SEW2871 inhibited inflammation-related cytokine expression, including PTGS-2, IL-1β, TNF-α and TGF-β1, more effectively compared with FTY720. Lymphopaenia was mainly caused by FTY720, whereas SEW2871 had a lesser effect. Both FTY720 and SEW2871 significantly reduced CD45+ cells (P = 0.002 and P = 0.032, respectively) and F4/80+ cells (P < 0.001 and P = 0.004, respectively) infiltration into the lesions, with FTY720 exerting a strong regulatory effect on CD4+ T cells. ConclusionsThis study suggests that S1P receptor 1 could be investigated as a potential novel therapeutic target for endometriosis in the future.