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. 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

Agnieszka Wlodarczyk  1   2 , Reza Khorooshi  1   2 , Joanna Marczynska  1   2 , Inge R Holtman  3 , Mark Burton  4 , Kirstine Nolling Jensen  1   2 , Morten Blaabjerg  1   2   5 , Morten Meyer  1   2 , Mads Thomassen  4 , Bart J L Eggen  2 , Nasrin Asgari  1   2   6 , Trevor Owens  1   2
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Type I interferon-activated microglia are critical for neuromyelitis optica pathology

Agnieszka Wlodarczyk et al. Glia. 2021 Apr.

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+ 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.

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

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References

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