IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis
IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis
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DOI：
10.1016/j.jneuroim.2019.04.011
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发表时间：
2019-07-15
影响因子：
3.3
通讯作者：
Townsend, Michael J.
中科院分区：
文献类型：
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作者：
Setiadi, A. Francesca;Abbas, Alexander R.;Townsend, Michael J.
IL-17与多发性硬化症（MS）的发病机制有关。本研究表明，阻断IL-17A而非IL-17F可减轻实验性自身免疫性脑脊髓炎（EAE）。我们进一步发现，复发-缓解型多发性硬化症（RRMS）患者脑脊液中IL-17A水平升高，并且与脑脊液/血清白蛋白商（Qalb）相关，后者是衡量血脑屏障（BBB）功能障碍的指标。然后，我们证明了IL-17A和IL-6的结合降低了血脑屏障细胞系hCMEC/D3中紧密连接（TJ）相关基因的表达，并破坏了单层完整性。然而，与IL-17A不同，RRMS患者CSF中的IL-6与Qalb无关。这些数据强调了靶向IL-17A在保持RRMS血脑屏障完整性方面的潜在重要性。
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.