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Immunology. 2018 Sep;155(1):112-122. doi: 10.1111/imm.12934. Epub 2018 May 10.

MicroRNA signature of central nervous system-infiltrating dendritic cells in an animal model of multiple sclerosis.

Author information

1
Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
2
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
3
The Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA.
4
Genome Technology Access Center, Washington University School of Medicine, St Louis, MO, USA.
5
Department of Immunology & Pathology, Washington University School of Medicine, St Louis, MO, USA.
6
Center for the Study of Itch, Washington University School of Medicine, St Louis, MO, USA.

Abstract

Innate immune cells are integral to the pathogenesis of several diseases of the central nervous system (CNS), including multiple sclerosis (MS). Dendritic cells (DCs) are potent CD11c+ antigen-presenting cells that are critical regulators of adaptive immune responses, particularly in autoimmune diseases such as MS. The regulation of DC function in both the periphery and CNS compartment has not been fully elucidated. One limitation to studying the role of CD11c+ DCs in the CNS is that microglia can upregulate CD11c during inflammation, making it challenging to distinguish bone marrow-derived DCs (BMDCs) from microglia. Selective expression of microRNAs (miRNAs) has been shown to distinguish populations of innate cells and regulate their function within the CNS during neuro-inflammation. Using the experimental autoimmune encephalomyelitis (EAE) murine model of MS, we characterized the expression of miRNAs in CD11c+ cells using a non-biased murine array. Several miRNAs, including miR-31, were enriched in CD11c+ cells within the CNS during EAE, but not LysM+ microglia. Moreover, to distinguish CD11c+ DCs from microglia that upregulate CD11c, we generated bone marrow chimeras and found that miR-31 expression was specific to BMDCs. Interestingly, miR-31-binding sites were enriched in mRNAs downregulated in BMDCs that migrated into the CNS, and a subset was confirmed to be regulated by miR-31. Finally, miR-31 was elevated in DCs migrating through an in vitro blood-brain barrier. Our findings suggest miRNAs, including miR-31, may regulate entry of DCs into the CNS during EAE, and could potentially represent therapeutic targets for CNS autoimmune diseases such as MS.

KEYWORDS:

dendritic cells; microRNAs; multiple sclerosis; neuroinflammation

PMID:
29749614
PMCID:
PMC6099169
DOI:
10.1111/imm.12934
[Indexed for MEDLINE]
Free PMC Article

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