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Authors: Hauptmann, Judith
Johann, Lisa
Marini, Federico
Kitic, Maja
Colombo, Elisa
Mufazalov, Ilgiz A.
Krueger, Martin
Karram, Khalad
Moos, Sonja
Wanke, Florian
Kurschus, Florian C.
Klein, Matthias
Cardoso, Silvia
Strauß, Judith
Bolisetty, Subhashini
Lühder, Fred
Schwaninger, Markus
Binder, Harald
Bechman, Ingo
Bopp, Tobias
Agarwal, Anupam
Soares, Miguel P.
Regen, Tommy
Waisman, Ari
Title: Interleukin-1 promotes autoimmune neuroinflammation by suppressing endothelial heme oxygenase-1 at the blood–brain barrier
Online publication date: 7-May-2021
Language: english
Abstract: The proinflammatory cytokine interleukin 1 (IL-1) is crucially involved in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Herein, we studied the role of IL-1 signaling in blood–brain barrier (BBB) endothelial cells (ECs), astrocytes and microglia for EAE development, using mice with the conditional deletion of its signaling receptor IL-1R1. We found that IL-1 signaling in microglia and astrocytes is redundant for the development of EAE, whereas the IL-1R1 deletion in BBB-ECs markedly ameliorated disease severity. IL-1 signaling in BBB-ECs upregulated the expression of the adhesion molecules Vcam-1, Icam-1 and the chemokine receptor Darc, all of which have been previously shown to promote CNS-specific inflammation. In contrast, IL-1R1 signaling suppressed the expression of the stress-responsive heme catabolizing enzyme heme oxygenase-1 (HO-1) in BBB-ECs, promoting disease progression via a mechanism associated with deregulated expression of the IL-1-responsive genes Vcam1, Icam1 and Ackr1 (Darc). Mechanistically, our data emphasize a functional crosstalk of BBB-EC IL-1 signaling and HO-1, controlling the transcription of downstream proinflammatory genes promoting the pathogenesis of autoimmune neuroinflammation.
DDC: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: Acta neuropathologica
Pages or article number: 549
Publisher: Springer
Publisher place: Berlin u.a.
Issue date: 2020
ISSN: 1432-0533
Publisher URL:
Publisher DOI: 10.1007/s00401-020-02187-x
Appears in collections:JGU-Publikationen

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