Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/13395
Title: MicroRNA-155 plays selective cell-intrinsic roles in brain-infiltrating immune cell populations during neuroinflammation
Authors: Thompson, J.W.
Hu, R.
Huffaker, T.B.
Ramstead, A.G.
Ekiz, Hüseyin Atakan
Bauer, K.M.
Tang, W.W.
Keywords: microRNA
Mirn155 microRNA, mouse
animal
brain
C57BL mouse
experimental autoimmune encephalomyelitis
knockout mouse
metabolism
mouse
multiple sclerosis
pathology
Th17 cell
Animals
Brain
Encephalomyelitis, Autoimmune, Experimental
Mice
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs
Multiple Sclerosis
Neuroinflammatory Diseases
Th17 Cells
Issue Date: 2023
Publisher: American Association of Immunologists
Abstract: The proinflammatory microRNA-155 (miR-155) is highly expressed in the serum and CNS lesions of patients with multiple sclerosis (MS). Global knockout (KO) of miR-155 in mice confers resistance to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), by reducing the encephalogenic potential of CNS-infiltrating Th17 T cells. However, cell-intrinsic roles for miR-155 during EAE have not been formally determined. In this study, we use single-cell RNA sequencing and cell-specific conditional miR-155 KOs to determine the importance of miR-155 expression in distinct immune cell populations. Time-course single-cell sequencing revealed reductions in T cells, macrophages, and dendritic cells (DCs) in global miR-155 KO mice compared with wild-type controls at day 21 after EAE induction. Deletion of miR-155 in T cells, driven by CD4 Cre, significantly reduced disease severity similar to global miR-155 KOs. CD11c Cre-mediated deletion of miR-155 in DCs also resulted in a modest yet significant reduction in the development of EAE, with both T cell- and DC-specific KOs showing a reduction in Th17 T cell infiltration into the CNS. Although miR-155 is highly expressed in infiltrating macrophages during EAE, deletion of miR-155 using LysM Cre did not impact disease severity. Taken together, these data show that although miR-155 is highly expressed in most infiltrating immune cells, miR-155 has distinct roles and requirements depending on the cell type, and we have demonstrated this using the gold standard conditional KO approach. This provides insights into which functionally relevant cell types should be targeted by the next generation of miRNA therapeutics. Copyright © 2023 by The American Association of Immunologists, Inc.
URI: https://doi.org/10.4049/jimmunol.2200478
https://hdl.handle.net/11147/13395
ISSN: 0022-1767
Appears in Collections:PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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