Anlotinib attenuates experimental autoimmune encephalomyelitis mice model of multiple sclerosis 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. 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 , decreased the phosphorylation of STAT3, and reduced the expression of . 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 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.