MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis

Nat Commun. 2015 May 12;6:7096. doi: 10.1038/ncomms8096.

Abstract

Although different autoimmune diseases show discrete clinical features, there are common molecular pathways intimately involved. Here we show that miR-125a is downregulated in peripheral CD4(+) T cells of human autoimmune diseases including systemic lupus erythematosus and Crohn's disease, and relevant autoimmune mouse models. miR-125a stabilizes both the commitment and immunoregulatory capacity of Treg cells. In miR-125a-deficient mice, the balance appears to shift from immune suppression to inflammation, and results in more severe pathogenesis of colitis and experimental autoimmune encephalomyelitis (EAE). The genome-wide target analysis reveals that miR-125a suppresses several effector T-cell factors including Stat3, Ifng and Il13. Using a chemically synthesized miR-125a analogue, we show potential to re-programme the immune homeostasis in EAE models. These findings point to miR-125a as a critical factor that controls autoimmune diseases by stabilizing Treg-mediated immune homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • Colitis / metabolism
  • Colitis / pathology
  • Crohn Disease
  • Down-Regulation
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Homeostasis
  • Humans
  • Immunity, Cellular / physiology*
  • Lupus Erythematosus, Systemic
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neuritis, Autoimmune, Experimental / metabolism
  • Neuritis, Autoimmune, Experimental / pathology
  • T-Lymphocytes, Regulatory / physiology*

Substances

  • Homeodomain Proteins
  • MIRN125 microRNA, human
  • MicroRNAs
  • Mirn125 microRNA, mouse
  • RAG-1 protein