Anlotinib attenuates experimental autoimmune encephalomyelitis mice model of multiple sclerosis via modulating the differentiation of Th17 and Treg cells

Background In multiple sclerosis (MS), the imbalance between T helper (Th)-17 cells and regulatory T (Treg) cells are critical in autoimmune central nervous system (CNS) inflammation and demyelination. Experimental autoimmune encephalomyelitis (EAE) is an established mouse MS model and simulates MS at diverse levels. Objectives This study aims at investigating the impact of anlotinib on the clinical severity of EAE and CD4(+) T cell differentiation. Materials and methods EAE-induced mice were treated with water (control) or 6 mg/kg anlotinib by gavage daily. At the peak of EAE, histopathological examination and flow cytometry analysis of CNS-infiltrating CD4(+) T cells were performed. In vitro differentiation of CD4(+) T cells under different conditions was detected by flow cytometry and quantitative real-time PCR. Finally, the impacts of anlotinib on the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the transcription levels of key genes involved in Th17 and Treg differentiation were tested. Results Anlotinib attenuated the clinical severity of EAE and changed the frequencies of CNS-infiltrating CD4(+) T cell subsets. Anlotinib inhibited the differentiation of Th17 cells in vitro, decreased the phosphorylation of STAT3, and reduced the expression of Rorc. Anlotinib promoted the differentiation of Treg cells and upregulated the expression levels of CD39 and CD73. Discussion and conclusions Anlotinib alleviated the symptoms of EAE via inhibiting the Th17 cell differentiation and promoting Treg cell differentiation. Our study provides new opportunities for the exploitation of anlotinib as a therapeutic agent for the treatment of MS.