Anlotinib attenuates experimental autoimmune encephalomyelitis mice model of multiple sclerosis via modulating the differentiation of Th17 and Treg cells. (4th July 2022)

• Record Type: Journal Article
• Authors: Zhu, Haoran; Li, Guangliang; Yin, Jie; Zhang, Hong; Da, Yurong; Li, Long
• Is Part Of: Immunopharmacology and immunotoxicology. Volume 44:Number 4(2022)
• Page Start: 594
• Page End: 602
• Publication Date: 2022-07-04
• Subjects: Anlotinib -- multiple sclerosis -- EAE -- Th17 differentiation -- Treg differentiation; Immunopharmacology -- Periodicals; Immunotoxicology -- Periodicals; Antibody-toxin conjugates -- Periodicals; Immunology -- Periodicals; 615.37
• DOI: 10.1080/08923973.2022.2071722
• Languages: English
• ISSNs: 0892-3973

Abstract

Abstract: 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.