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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

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

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  • Medientyp: E-Artikel
  • Titel: Interleukin-1 promotes autoimmune neuroinflammation by suppressing endothelial heme oxygenase-1 at the blood–brain barrier
  • Beteiligte: 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
  • Erschienen: Springer Science and Business Media LLC, 2020
  • Erschienen in: Acta Neuropathologica, 140 (2020) 4, Seite 549-567
  • Sprache: Englisch
  • DOI: 10.1007/s00401-020-02187-x
  • ISSN: 0001-6322; 1432-0533
  • Entstehung:
  • Hochschulschrift:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 <jats:italic>Vcam1</jats:italic>, <jats:italic>Icam1</jats:italic> and <jats:italic>Ackr1</jats:italic> (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.</jats:p>