Tanshinone IIA Ameliorates CNS Autoimmunity by Promoting the Differentiation of Regulatory T Cells

Tanshinone IIA (TSA), an important natural lipophilic diterpene compound from the traditional Chinese herb Salvia miltiorrhiza Bunge, has long been widely used for the prevention and treatment of various diseases because of its anti-inflammatory activities; however, the anti-inflammatory mechanism remains unknown. In the present work, we examined the effects of TSA on experimental autoimmune encephalomyelitis (EAE), a model of autoreactive T/B cell-mediated central nervous system (CNS) autoimmunity. The data showed that TSA significantly attenuates the severity of EAE when administered at the pre-onset and peak of clinical disease. In vivo, the protective effects of TSA on EAE mice are correlated with diminished inflammatory infiltration, demyelination, and GM-CSF-producing CD4⁺ T cells in the spinal cord and selectively increased regulatory T (Treg) cell frequencies in both the spinal cord and spleen. We further confirm that TSA can promote the polarization of naïve CD4⁺ T cells into Treg cells both by targeting dendritic cells (DCs) to drive transforming growth factor β1 (TGF-β1) upregulation and by directly targeting naïve CD4⁺ T cells in vitro. Most importantly, we showed that TSA-induced Treg cells display an effective suppressive activity at a level comparable to TGF-β1-polarized Treg Cells in vitro and in vivo. Taken together, our data provide evidence that TSA can promote Treg cell differentiation, and TSA may have a promising application as a therapeutic agent for the treatment of neuroinflammatory diseases.