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


Journal

Journal of neuroimmunology
ISSN: 1872-8421
Titre abrégé: J Neuroimmunol
Pays: Netherlands
ID NLM: 8109498

Informations de publication

Date de publication:
15 07 2019
Historique:
received: 24 12 2018
revised: 18 04 2019
accepted: 19 04 2019
pubmed: 30 4 2019
medline: 31 3 2020
entrez: 30 4 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31034962
pii: S0165-5728(18)30579-4
doi: 10.1016/j.jneuroim.2019.04.011
pii:
doi:

Substances chimiques

IL17A protein, human 0
IL17F protein, human 0
IL6 protein, human 0
Il17a protein, mouse 0
Interleukin-17 0
Interleukin-6 0
Receptors, Interleukin-6 0
Recombinant Proteins 0

Types de publication

Comparative Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

147-154

Informations de copyright

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

Auteurs

A Francesca Setiadi (AF)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Alexander R Abbas (AR)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Surinder Jeet (S)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Kit Wong (K)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Antje Bischof (A)

Weill Institute for Neurosciences, Department of Neurology, UCSF, 675 Nelson Rising Lane, San Francisco, California 94158, USA; Neurology and Neurologic Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.

Ivan Peng (I)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

James Lee (J)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Meire Bremer (M)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Erica L Eggers (EL)

Weill Institute for Neurosciences, Department of Neurology, UCSF, 675 Nelson Rising Lane, San Francisco, California 94158, USA.

Jason DeVoss (J)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Tracy Staton (T)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Ann Herman (A)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

H-Christian von Büdingen (HC)

Weill Institute for Neurosciences, Department of Neurology, UCSF, 675 Nelson Rising Lane, San Francisco, California 94158, USA.

Michael J Townsend (MJ)

Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: townsem1@gene.com.

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Classifications MeSH