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Wlodarczyk A, Khorooshi R, Marczynska J, et al. Type I interferon-activated microglia are critical for neuromyelitis optica pathology. Glia. 2020;69(4):943-953doi: 10.1002/glia.23938.
Wlodarczyk, A., Khorooshi, R., Marczynska, J., Holtman, I. R., Burton, M., Jensen, K. N., Blaabjerg, M., Meyer, M., Thomassen, M., Eggen, B. J. L., Asgari, N., & Owens, T. (2021). Type I interferon-activated microglia are critical for neuromyelitis optica pathology. Glia, 69(4), 943-953. https://doi.org/10.1002/glia.23938
Wlodarczyk, Agnieszka, et al. "Type I interferon-activated microglia are critical for neuromyelitis optica pathology." Glia vol. 69,4 (2021): 943-953. doi: https://doi.org/10.1002/glia.23938
Wlodarczyk A, Khorooshi R, Marczynska J, Holtman IR, Burton M, Jensen KN, Blaabjerg M, Meyer M, Thomassen M, Eggen BJL, Asgari N, Owens T. Type I interferon-activated microglia are critical for neuromyelitis optica pathology. Glia. 2021 Apr;69(4):943-953. doi: 10.1002/glia.23938. Epub 2020 Nov 26. PMID: 33241604.
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Glia. 2021 Apr;69(4):943-953. doi: 10.1002/glia.23938. Epub 2020 Nov 26.

Type I interferon-activated microglia are critical for neuromyelitis optica pathology.

Glia

Agnieszka Wlodarczyk, Reza Khorooshi, Joanna Marczynska, Inge R Holtman, Mark Burton, Kirstine Nolling Jensen, Morten Blaabjerg, Morten Meyer, Mads Thomassen, Bart J L Eggen, Nasrin Asgari, Trevor Owens

Affiliations

  1. Department of Neurobiology Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
  2. Brain Research InterDisciplinary Guided Excellence (BRIDGE), University of Southern Denmark, Denmark.
  3. Department of Biomedical Sciences of Cells and Systems, Section Molecular Neurobiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  4. Department of Genetics, Odense University Hospital, Odense, Denmark.
  5. Department of Neurology, Odense University Hospital and Neurology Research Unit, Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark.
  6. Department of Neurology, Slagelse Hospital, Slagelse, Denmark.

PMID: 33241604 DOI: 10.1002/glia.23938

Abstract

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system (CNS) most frequently mediated by serum autoantibodies against the water channel aquaporin 4, expressed on CNS astrocytes, resulting in primary astrocytopathy. There is no cure for NMO, and treatment with Type I interferon (IFNI)-IFNβ 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 IFNβ. 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 IFNβ led to exacerbated pathology and further microglial activation as evidenced by expansion of a CD11c

© 2020 Wiley Periodicals LLC.

Keywords: CD11c+ microglia; Type I interferon; depletion; microglia; neuromyelitis optica

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