Extracellular MicroRNA signature of human helper T cell subsets in health and autoimmunity

Anna Torri, Donatella Carpi, Elisabetta Bulgheroni, Maria Cristina Crosti, Monica Moro, Paola Gruarin, Riccardo L. Rossi, Grazisa Rossetti, Dolores Di Vizio, Mirjam Hoxha, Valentina Bollati, Cristina Gagliani, Carlo Tacchetti, Moira Paroni, Jens Geginat, Laura Corti, Luigia Venegoni, Emilio Berti, Massimiliano Pagani, Giuseppe MatareseSergio Abrignani, Paola De Candia

Research output: Contribution to journalArticle

Abstract

Upon T cell receptor stimulation, CD4 ô T helper (Th) lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro T cell receptor stimulation of Th1, Th17, and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared with those released by the other subsets. In particular, miR-146a-5p, miR-150-5p, and miR-21-5p are enriched, whereas miR-106a-5p, miR-155-5p, and miR-19a-3p are depleted in Treg-derived EVs. The in vitro identified EV-associated microRNA signature was increased in serum of autoimmune patients with psoriasis and returned to healthy levels upon effective treatment with etanercept, a biological drug targeting the TNF pathway and suppressing inflammation. Moreover, Gene Set Enrichment Analysis showed an over-representation of genes relevant for T cell activation, such as CD40L, IRAK1, IRAK2, STAT1, and c-Myb in the list of validated targets of Treg-derived EV miRNAs. At functional level, Treg-derived (but not Th1/ Th17-derived) EVs inhibited CD4 + T cell proliferation and suppressed two relevant targets of miR-146a-5p: STAT1 and IRAK2. In conclusion, our work identified the miRNAs specifically released by different human CD4 + T cell subsets and started to unveil the potential use of their quantity in human serum to mark the pathological elicitation of these cells in vivo and their biological effect in cell to cell communication during the adaptive immune response.

Original languageEnglish
Pages (from-to)2903-2915
Number of pages13
JournalJournal of Biological Chemistry
Volume292
Issue number7
DOIs
Publication statusPublished - Feb 17 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Torri, A., Carpi, D., Bulgheroni, E., Crosti, M. C., Moro, M., Gruarin, P., Rossi, R. L., Rossetti, G., Vizio, D. D., Hoxha, M., Bollati, V., Gagliani, C., Tacchetti, C., Paroni, M., Geginat, J., Corti, L., Venegoni, L., Berti, E., Pagani, M., ... De Candia, P. (2017). Extracellular MicroRNA signature of human helper T cell subsets in health and autoimmunity. Journal of Biological Chemistry, 292(7), 2903-2915. https://doi.org/10.1074/jbc.M116.769893