Institute of Infection and Immunity and Translational Medical Center, Huaihe Hospital of Henan University, Kaifeng 475000, China; College of Life Science, Henan University, Kaifeng 475000, China.
Institute of Infection and Immunity and Translational Medical Center, Huaihe Hospital of Henan University, Kaifeng 475000, China; School of Basic Medical Sciences, Henan University, Kaifeng 475000, China.
J Nutr Biochem. 2021 Mar;89:108560. doi: 10.1016/j.jnutbio.2020.108560. Epub 2020 Nov 26.
Targeting pathogenic immune cell trafficking poses an attractive opportunity to attenuate autoimmune disorders such as multiple sclerosis (MS). MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are characterized by the immune cells-mediated demyelination and neurodegeneration of the central nervous system (CNS). Our previous study has proven that dietary naringenin ameliorates EAE clinical symptoms via reducing the CNS cell infiltration. The present study examined the beneficial effects of naringenin on maintaining the blood-brain barrier in EAE mice via dietary naringenin intervention. The results showed that naringenin-treated EAE mice had an intact blood-CNS barrier by increasing tight junction-associated factors and decreasing Evans Blue dye in the CNS. Naringenin decreased the accumulation and maturation of conventional dendritic cells (cDCs), CCL19, and CCR7 in the CNS. Also, naringenin blocked the chemotaxis and antigen-presenting function of cDCs that resulted in reducing T-cell secreting cytokines (IFN-γ, IL-17, and IL-6) in the spleen. Importantly, naringenin blocked pathogenic T cells infiltrated into the CNS and attenuates passive EAE. Therefore, by blocking chemokine-mediated migration of DCs and pathogenic T cells into the CNS, naringenin attenuates EAE pathogenesis and might be a potential candidate for the treatment of autoimmune diseases, such as MS and other chronic T-cell mediated autoimmune diseases.
靶向致病性免疫细胞迁移为减轻多发性硬化症（MS）等自身免疫性疾病提供了一个有吸引力的机会。MS 及其动物模型实验性自身免疫性脑脊髓炎（EAE）的特征是免疫细胞介导的中枢神经系统（CNS）脱髓鞘和神经退行性变。我们之前的研究已经证明，饮食中的柚皮素通过减少中枢神经系统细胞浸润来改善 EAE 的临床症状。本研究通过饮食柚皮素干预检查了柚皮素对维持 EAE 小鼠血脑屏障的有益作用。结果表明，柚皮素处理的 EAE 小鼠通过增加紧密连接相关因子和减少中枢神经系统中的 Evans Blue 染料，具有完整的血脑屏障。柚皮素减少了中枢神经系统中常规树突状细胞（cDC）、CCL19 和 CCR7 的积累和成熟。此外，柚皮素阻断了 cDC 的趋化作用和抗原呈递功能，导致脾脏中 T 细胞分泌的细胞因子（IFN-γ、IL-17 和 IL-6）减少。重要的是，柚皮素阻断了致病性 T 细胞浸润中枢神经系统并减轻了被动 EAE。因此，通过阻断趋化因子介导的 DC 和致病性 T 细胞向中枢神经系统的迁移，柚皮素减轻了 EAE 的发病机制，可能是治疗多发性硬化症和其他慢性 T 细胞介导的自身免疫性疾病等自身免疫性疾病的潜在候选药物。
