Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells

Chiara Cossetti, Nunzio Iraci, Tim R. Mercer, Tommaso Leonardi, Emanuele Alpi, Denise Drago, Clara Alfaro-Cervello, Harpreet K. Saini, Matthew P. Davis, Julia Schaeffer, Beatriz Vega, Matilde Stefanini, CongJian Zhao, Werner Muller, Jose Manuel Garcia-Verdugo, Suresh Mathivanan, Angela Bachi, Anton J. Enright, John S. Mattick, Stefano Pluchino

Research output: Contribution to journalArticlepeer-review

Abstract

The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. Wedescribed induction of interferon gamma (IFN-γ) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-γ bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-γ/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-γ/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system.

Original languageEnglish
Pages (from-to)193-204
Number of pages12
JournalMolecular Cell
Volume56
Issue number2
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells'. Together they form a unique fingerprint.

Cite this