白细胞介素 17A 与复发缓解型多发性硬化症中血脑屏障的破坏有关。
IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis.
机构信息
Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Weill Institute for Neurosciences, Department of Neurology, UCSF, 675 Nelson Rising Lane, San Francisco, California 94158, USA; Neurology and Neurologic Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.
出版信息
J Neuroimmunol. 2019 Jul 15;332:147-154. doi: 10.1016/j.jneuroim.2019.04.011. Epub 2019 Apr 21.
IL-17 has been implicated in the pathogenesis of multiple sclerosis (MS). Here, we show that blockade of IL-17A, but not IL-17F, attenuated experimental autoimmune encephalomyelitis (EAE). We further show that IL-17A levels were elevated in the CSF of relapsing-remitting MS (RRMS) patients and that they correlated with the CSF/serum albumin quotient (Qalb), a measure of blood-brain barrier (BBB) dysfunction. We then demonstrated that the combination of IL-17A and IL-6 reduced the expression of tight junction (TJ)-associated genes and disrupted monolayer integrity in the BBB cell line hCMEC/D3. However, unlike IL-17A, IL-6 in the CSF from RRMS patients did not correlate with Qalb. These data highlight the potential importance of targeting IL-17A in preserving BBB integrity in RRMS.
IL-17 已被牵连到多发性硬化症（MS）的发病机制中。在这里，我们表明阻断 IL-17A 而不是 IL-17F 可减轻实验性自身免疫性脑脊髓炎（EAE）。我们进一步表明，IL-17A 水平在复发性缓解型多发性硬化症（RRMS）患者的脑脊液中升高，并且与脑脊液/血清白蛋白比率（Qalb）相关，这是血脑屏障（BBB）功能障碍的衡量标准。然后，我们证明 IL-17A 和 IL-6 的组合降低了紧密连接（TJ）相关基因的表达，并破坏了 BBB 细胞系 hCMEC/D3 的单层完整性。然而，与 IL-17A 不同，RRMS 患者脑脊液中的 IL-6 与 Qalb 不相关。这些数据强调了靶向 IL-17A 以维持 RRMS 中 BBB 完整性的重要性。
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