Intracellular modulation, extracellular disposal and serum increase of MiR-150 mark lymphocyte activation

PLoS One. 2013 Sep 26;8(9):e75348. doi: 10.1371/journal.pone.0075348. eCollection 2013.

Abstract

Activated lymphocytes release nano-sized vesicles (exosomes) containing microRNAs that can be monitored in the bloodstream. We asked whether elicitation of immune responses is followed by release of lymphocyte-specific microRNAs. We found that, upon activation in vitro, human and mouse lymphocytes down-modulate intracellular miR-150 and accumulate it in exosomes. In vivo, miR-150 levels increased significantly in serum of humans immunized with flu vaccines and in mice immunized with ovalbumin, and this increase correlated with elevation of antibody titers. Immunization of immune-deficient mice, lacking MHCII, resulted neither in antibody production nor in elevation of circulating miR-150. This study provides proof of concept that serum microRNAs can be detected, with minimally invasive procedure, as biomarkers of vaccination and more in general of adaptive immune responses. Furthermore, the prompt reduction of intracellular level of miR-150, a key regulator of mRNAs critical for lymphocyte differentiation and functions, linked to its release in the external milieu suggests that the selective extracellular disposal of microRNAs can be a rapid way to regulate gene expression during lymphocyte activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • CD4-Positive T-Lymphocytes / physiology
  • Cluster Analysis
  • Endosomes / metabolism
  • Extracellular Space / metabolism
  • Gene Expression Profiling
  • Humans
  • Intracellular Space / metabolism
  • Lymphocyte Activation / physiology*
  • Mice
  • Mice, Knockout
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Vaccination

Substances

  • MIRN150 microRNA, human
  • MicroRNAs
  • Mirn150 microRNA, mouse

Grant support

This research was supported by a CARIPLO grant (N° 2009-3603) http://www.fondazionecariplo.it; by an ERC advanced grant to SA (N° 269022) http://erc.europa.eu; and by Fondazione Invernizzi. This study was also supported (in part) by research funding to GC from AIRC (IG11523) http://www.airc.it/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.