4.3 Article

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

Journal

JOURNAL OF NEUROIMMUNOLOGY
Volume 332, Issue -, Pages 147-154

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2019.04.011

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Funding

  1. Genentech, a member of the Roche Group

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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.

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