(R)-Salbutamol Improves Imiquimod-Induced Psoriasis-Like Skin Dermatitis by Regulating the Th17/Tregs Balance and Glycerophospholipid Metabolism.

Psoriasis is a skin disease that is characterized by a high degree of inflammation caused by immune dysfunction. ()-salbutamol is a bronchodilator for asthma and was reported to alleviate immune system reactions in several diseases. In this study, using imiquimod (IMQ)-induced mouse psoriasis-like dermatitis model, we evaluated the therapeutic effects of ()-salbutamol in psoriasis in vivo, and explored the metabolic pathway involved. The results showed that, compared with IMQ group, ()-salbutamol treatment significantly ameliorated psoriasis, reversed the suppressive effects of IMQ on differentiation, extreme keratinocyte proliferation, and infiltration of inflammatory cells. Enzyme-linked immunosorbent assays (ELISA) showed that ()-salbutamol markedly reduced the plasma levels of IL-17. Cell analysis using flow cytometry showed that ()-salbutamol decreased the proportion of CD4+ Th17+ T cells (Th17), whereas it increased the percentage of CD25+ Foxp3+ regulatory T cells (Tregs) in the spleens. ()-salbutamol also decreased the weight ratio of spleen to body. Furthermore, untargeted metabolomics showed that ()-salbutamol affected three metabolic pathways, including (i) arachidonic acid metabolism, (ii) sphingolipid metabolism, and (iii) glycerophospholipid metabolism. These results demonstrated that ()-salbutamol can alleviate IMQ-induced psoriasis through regulating Th17/Tregs cell response and glycerophospholipid metabolism. It may provide a new use of ()-salbutamol in the management of psoriasis.