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IL-17A is associated with the breakdown of the blood-brain barrier in relapsing-remitting multiple sclerosis

Setiadi, AF;Abbas, AR;Jeet, S;Wong, K;Bischof, A;Peng, I;Lee, J;Bremer, M;Eggers, EL;DeVoss, J;Staton, T;Herman, A;von Bdingen, HC;Townsend, MJ;

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. Copyright 2019 The Authors. Published by Elsevier B.V. All rights reserved.