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

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...

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Bibliographic Details
Published in:Journal of neuroimmunology 2019-07, Vol.332, p.147-154
Main Authors: Setiadi, A. Francesca, Abbas, Alexander R., Jeet, Surinder, Wong, Kit, Bischof, Antje, Peng, Ivan, Lee, James, Bremer, Meire, Eggers, Erica L., DeVoss, Jason, Staton, Tracy, Herman, Ann, von Büdingen, H. -Christian, Townsend, Michael J.
Format: Article
Language:English
Subjects:
Adult
Aged
Animals
Blood-Brain Barrier
Cells, Cultured
Encephalomyelitis, Autoimmune, Experimental - physiopathology
Encephalomyelitis, Autoimmune, Experimental - therapy
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Female
Humans
Immunization, Passive
Interleukin-17 - antagonists & inhibitors
Interleukin-17 - cerebrospinal fluid
Interleukin-17 - physiology
Interleukin-6 - pharmacology
Mice
Mice, Inbred C57BL
Middle Aged
Multiple Sclerosis, Relapsing-Remitting - cerebrospinal fluid
Multiple Sclerosis, Relapsing-Remitting - physiopathology
Receptors, Interleukin-6 - physiology
Recombinant Proteins - pharmacology
Young Adult
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Summary: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. [Display omitted] •IL-17A, but not IL-17F, contributes to EAE pathogenesis.•IL-17A, but not IL-17F, is elevated in RRMS CSF.•CSF IL-17A levels correlate with blood-brain barrier damage in RRMS.•A combination of IL-17A and IL6 impairs endothelium tight junction gene expression and monolayer integrity.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2019.04.011