| Literature DB >> 25242146 |
Chiara Cossetti1, Nunzio Iraci1, Tim R Mercer2, Tommaso Leonardi3, Emanuele Alpi4, Denise Drago4, Clara Alfaro-Cervello1, Harpreet K Saini5, Matthew P Davis5, Julia Schaeffer1, Beatriz Vega1, Matilde Stefanini1, CongJian Zhao6, Werner Muller7, Jose Manuel Garcia-Verdugo8, Suresh Mathivanan9, Angela Bachi4, Anton J Enright5, John S Mattick10, Stefano Pluchino11.
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. We described 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.Entities:
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Year: 2014 PMID： 25242146 PMCID： PMC4578249 DOI： 10.1016/j.molcel.2014.08.020
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970