Intracellular Modulation, Extracellular Disposal and Serum Increase of MiR-150 Mark Lymphocyte Activation

Paola de Candia, Anna Torri, Tatiana Gorletta, Maya Fedeli, Elisabetta Bulgheroni, Cristina Cheroni, Francesco Marabita, Mariacristina Crosti, Monica Moro, Elena Pariani, Luisa Romanò, Susanna Esposito, Fabio Mosca, Grazisa Rossetti, Riccardo L. Rossi, Jens Geginat, Giulia Casorati, Paolo Dellabona, Massimiliano Pagani, Sergio Abrignani

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numbere75348
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 26 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    de Candia, P., Torri, A., Gorletta, T., Fedeli, M., Bulgheroni, E., Cheroni, C., Marabita, F., Crosti, M., Moro, M., Pariani, E., Romanò, L., Esposito, S., Mosca, F., Rossetti, G., Rossi, R. L., Geginat, J., Casorati, G., Dellabona, P., Pagani, M., & Abrignani, S. (2013). Intracellular Modulation, Extracellular Disposal and Serum Increase of MiR-150 Mark Lymphocyte Activation. PLoS One, 8(9), [e75348]. https://doi.org/10.1371/journal.pone.0075348