Type I interferon-activated microglia are critical for neuromyelitis optica pathology
| Autor: | Agnieszka Wlodarczyk, Mads Thomassen, Bart J. L. Eggen, Morten Blaabjerg, Kirstine Nolling Jensen, Morten Meyer, Trevor Owens, Joanna Marczynska, Reza Khorooshi, Inge R. Holtman, Mark Burton, Nasrin Asgari |
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| Přispěvatelé: | Molecular Neuroscience and Ageing Research (MOLAR), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Central nervous system CD11c microglia neuromyelitis optica AQUAPORIN-4 Biology PLAYS Transcriptome Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Interferon REVEALS medicine Animals CELL Receptor Type I interferon CD11c(+) microglia BETA TREATMENT Aquaporin 4 Neuromyelitis optica Microglia depletion CENTRAL-NERVOUS-SYSTEM medicine.disease CD11c microglia 030104 developmental biology medicine.anatomical_structure Neurology Astrocytes Interferon Type I 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Glia, 69(4), 943-953. Wiley Wlodarczyk, A, Khorooshi, R M H, 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, vol. 69, no. 4, pp. 943-953 . https://doi.org/10.1002/glia.23938 |
| ISSN: | 0894-1491 |
| Popis: | 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)-IFN beta 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 beta. 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 beta led to exacerbated pathology and further microglial activation as evidenced by expansion of a CD11c(+) subset of microglia. Importantly, depletion of microglia led to suppression of pathology and decrease of IFNI signature genes. Our data show a pro-pathologic role for IFNI-activated microglia in NMO and open new perspectives for microglia-targeted therapies. |
| Databáze: | OpenAIRE |
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