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microRNA-17-92 regulates IL-10 production by regulatory T cells and control of experimental autoimmune encephalomyelitis.

  • Author(s): de Kouchkovsky, Dimitri
  • Esensten, Jonathan H
  • Rosenthal, Wendy L
  • Morar, Malika M
  • Bluestone, Jeffrey A
  • Jeker, Lukas T
  • et al.
Abstract

microRNAs (miRNA) are essential for regulatory T cell (Treg) function but little is known about the functional relevance of individual miRNA loci. We identified the miR-17-92 cluster as CD28 costimulation dependent, suggesting that it may be key for Treg development and function. Although overall immune homeostasis was maintained in mice with miR-17-92-deficient Tregs, expression of the miR-17-92 miRNA cluster was critical for Treg accumulation and function during an acute organ-specific autoimmune disease in vivo. Treg-specific loss of miR-17-92 expression resulted in exacerbated experimental autoimmune encephalitis and failure to establish clinical remission. Using peptide-MHC tetramers, we demonstrate that the miR-17-92 cluster was specifically required for the accumulation of activated Ag-specific Treg and for differentiation into IL-10-producing effector Treg.

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