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Herein, we studied the role of IL-1 signaling in blood\u2013brain 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>","DOI":"10.1007\/s00401-020-02187-x","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T04:35:11Z","timestamp":1594442111000},"page":"549-567","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Interleukin-1 promotes autoimmune neuroinflammation by suppressing endothelial heme oxygenase-1 at the blood\u2013brain barrier"],"prefix":"10.1007","volume":"140","author":[{"given":"Judith","family":"Hauptmann","sequence":"first","affiliation":[]},{"given":"Lisa","family":"Johann","sequence":"additional","affiliation":[]},{"given":"Federico","family":"Marini","sequence":"additional","affiliation":[]},{"given":"Maja","family":"Kitic","sequence":"additional","affiliation":[]},{"given":"Elisa","family":"Colombo","sequence":"additional","affiliation":[]},{"given":"Ilgiz A.","family":"Mufazalov","sequence":"additional","affiliation":[]},{"given":"Martin","family":"Krueger","sequence":"additional","affiliation":[]},{"given":"Khalad","family":"Karram","sequence":"additional","affiliation":[]},{"given":"Sonja","family":"Moos","sequence":"additional","affiliation":[]},{"given":"Florian","family":"Wanke","sequence":"additional","affiliation":[]},{"given":"Florian C.","family":"Kurschus","sequence":"additional","affiliation":[]},{"given":"Matthias","family":"Klein","sequence":"additional","affiliation":[]},{"given":"Silvia","family":"Cardoso","sequence":"additional","affiliation":[]},{"given":"Judith","family":"Strau\u00df","sequence":"additional","affiliation":[]},{"given":"Subhashini","family":"Bolisetty","sequence":"additional","affiliation":[]},{"given":"Fred","family":"L\u00fchder","sequence":"additional","affiliation":[]},{"given":"Markus","family":"Schwaninger","sequence":"additional","affiliation":[]},{"given":"Harald","family":"Binder","sequence":"additional","affiliation":[]},{"given":"Ingo","family":"Bechman","sequence":"additional","affiliation":[]},{"given":"Tobias","family":"Bopp","sequence":"additional","affiliation":[]},{"given":"Anupam","family":"Agarwal","sequence":"additional","affiliation":[]},{"given":"Miguel P.","family":"Soares","sequence":"additional","affiliation":[]},{"given":"Tommy","family":"Regen","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4304-8234","authenticated-orcid":false,"given":"Ari","family":"Waisman","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,7,11]]},"reference":[{"key":"2187_CR1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1002\/eji.201445125","volume":"45","author":"M Abadier","year":"2015","unstructured":"Abadier M, Haghayegh Jahromi N, Cardoso Alves L, Boscacci R, Vestweber D, Barnum S et al (2015) Cell surface levels of endothelial ICAM-1 influence the transcellular or paracellular T-cell diapedesis across the blood\u2013brain barrier. 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