6533b82cfe1ef96bd129012e

RESEARCH PRODUCT

Extracellular Vesicles from Neural Stem Cells Transfer IFN-γ via Ifngr1 to Activate Stat1 Signaling in Target Cells

Harpreet K SainiAngela BachiJulia SchaefferJulia SchaefferMatilde StefaniniMatilde StefaniniBeatriz VegaBeatriz VegaTommaso LeonardiDenise DragoEmanuele AlpiJohn S. MattickStefano PluchinoStefano PluchinoWerner MüllerCongjian ZhaoSuresh MathivananMatthew P. DavisTim R. MercerAnton J. EnrightJosé Manuel García-verdugoNunzio IraciNunzio IraciChiara CossettiClara Alfaro-cervelloClara Alfaro-cervello

subject

Cell signalingCell CommunicationBiologyArticle3T3 cellsProinflammatory cytokineInterferon-gammaMiceTh2 CellsNeural Stem CellsPrecursor cellmedicineAnimalsInterferon gammaRNA MessengerTransport VesiclesMolecular BiologyReceptors InterferonInflammationBiological Transport3T3 CellsCell BiologyTh1 CellsNeural stem cellCell biologySTAT1 Transcription Factormedicine.anatomical_structureCellular MicroenvironmentSignal transductionStem cellSignal Transductionmedicine.drug

description

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.

yearjournalcountryeditionlanguage
2014-11-01Molecular Cell
https://doi.org/10.1016/j.molcel.2014.11.009