Cutting Edge: MicroRNA-223 Regulates Myeloid Dendritic Cell-Driven Th17 Responses in Experimental Autoimmune Encephalomyelitis

J Immunol. 2016 Feb 15;196(4):1455-1459. doi: 10.4049/jimmunol.1501965. Epub 2016 Jan 18.

Abstract

Myeloid cells play a crucial role in the induction and sustained inflammation in neuroinflammatory disorders, such as multiple sclerosis. miR-223, a myeloid cell-specific microRNA, is one of the most upregulated microRNAs in multiple sclerosis patients. We demonstrate that miR-223-knockout mice display significantly reduced active and adoptive-transfer experimental autoimmune encephalomyelitis that is characterized by reduced numbers of myeloid dendritic cells (mDCs) and Th17 cells in the CNS. Knockout mDCs have increased PD-L1 and decreased IL-1β, IL-6, and IL-23 expression, as well as a reduced capacity to drive Th17, but not Th1, cell differentiation. Thus, miR-223 controls mDC-induced activation of pathologic Th17 responses during autoimmune inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Lymphocyte Activation
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Th1 Cells / immunology
  • Th17 Cells / immunology*

Substances

  • Cytokines
  • MIRN223 microRNA, mouse
  • MicroRNAs