Interleukin-1 promotes autoimmune neuroinflammation by suppressing endothelial heme oxygenase-1 at the blood–brain barrier

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Acta neuropathologica. - 140, 4 (2020) , 549-567, ISSN: 1432-0533

Classification and Topics

• Keyword: Blut-Hirn-Schranke ; Interleukin 1 ; Autoimmunität

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Hauptmann, Judith ; Johann, Lisa ; Marini, Federico ; Kitic, Maja ; Colombo, Elisa ; Mufazalov, Ilgiz A. ; Krueger, Martin ; Karram, Khalad ; Moos, Sonja ; Wanke, Florian ; Kurschus, Florian ; 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

Further information

• DOI: 10.1007/s00401-020-02187-x
• URN: urn:nbn:de:bsz:25-freidok-1675134
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:41 PM CET