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There is no cure for NMO, and treatment with Type I interferon (IFNI)\u2010IFN\u03b2 is ineffective or even detrimental. We have previously shown that both NMO lesions and associated microglial activation were reduced in mice lacking the receptor for IFN\u03b2. However, the role of microglia in NMO is not well understood. In this study, we clarify the pathomechanism for IFNI dependence of and the role of microglia in experimental NMO. Transcriptome analysis showed a strong IFNI footprint in affected CNS tissue as well as in microglial subpopulations. Treatment with IFN\u03b2 led to exacerbated pathology and further microglial activation as evidenced by expansion of a CD11c<jats:sup>+<\/jats:sup> subset of microglia. Importantly, depletion of microglia led to suppression of pathology and decrease of IFNI signature genes. Our data show a pro\u2010pathologic role for IFNI\u2010activated microglia in NMO and open new perspectives for microglia\u2010targeted therapies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/glia.23938","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T08:26:45Z","timestamp":1606379205000},"page":"943-953","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Type I interferon\u2010activated microglia are critical for neuromyelitis optica pathology"],"prefix":"10.1002","volume":"69","author":[{"given":"Agnieszka","family":"Wlodarczyk","sequence":"first","affiliation":[{"name":"Department of Neurobiology Research, Institute for Molecular Medicine University of Southern Denmark  Odense Denmark"},{"name":"Brain Research InterDisciplinary Guided Excellence (BRIDGE), University of Southern Denmark  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Khorooshi","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute for Molecular Medicine University of Southern Denmark  Odense Denmark"},{"name":"Brain Research InterDisciplinary Guided Excellence (BRIDGE), University of Southern Denmark  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Marczynska","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute for Molecular Medicine University of Southern Denmark  Odense Denmark"},{"name":"Brain Research InterDisciplinary Guided Excellence (BRIDGE), University of Southern Denmark  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge R.","family":"Holtman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Burton","sequence":"additional","affiliation":[{"name":"Department of Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstine Nolling","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute for Molecular Medicine University of Southern Denmark  Odense Denmark"},{"name":"Brain Research InterDisciplinary Guided Excellence (BRIDGE), University of Southern Denmark  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Blaabjerg","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute for Molecular Medicine University of Southern Denmark  Odense Denmark"},{"name":"Brain Research InterDisciplinary Guided Excellence (BRIDGE), University of Southern Denmark  Denmark"},{"name":"Department of Neurology, Odense University Hospital and Neurology Research Unit, Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute for Molecular Medicine University of Southern Denmark  Odense Denmark"},{"name":"Brain Research InterDisciplinary Guided Excellence (BRIDGE), University of Southern Denmark  Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Department of Genetics Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8941-0353","authenticated-orcid":false,"given":"Bart J. 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