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Merck

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

Journal of neuroimmunology (2019-04-30)
A Francesca Setiadi, Alexander R Abbas, Surinder Jeet, Kit Wong, Antje Bischof, Ivan Peng, James Lee, Meire Bremer, Erica L Eggers, Jason DeVoss, Tracy Staton, Ann Herman, H-Christian von Büdingen, Michael J Townsend
ABSTRAKT

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.