Journal article

TGF-beta inhibits the activation and functions of NK cells by repressing the mTOR pathway

Sebastien Viel, Antoine Marcais, Fernando Souza-Fonseca Guimaraes, Roisin Loftus, Jessica Rabilloud, Morgan Grau, Sophie Degouve, Sophia Djebali, Amelien Sanlaville, Emily Charrier, Jacques Bienvenu, Julien C Marie, Christophe Caux, Jacqueline Marvel, Liam Town, Nicholas D Huntington, Laurent Bartholin, David Finlay, Mark J Smyth, Thierry Walzer



Transforming growth factor-β (TGF-β) is a major immunosuppressive cytokine that maintains immune homeostasis and prevents autoimmunity through its antiproliferative and anti-inflammatory properties in various immune cell types. We provide genetic, pharmacologic, and biochemical evidence that a critical target of TGF-β signaling in mouse and human natural killer (NK) cells is the serine and threonine kinase mTOR (mammalian target of rapamycin). Treatment of mouse or human NK cells with TGF-β in vitro blocked interleukin-15 (IL-15)-induced activation of mTOR. TGF-β and the mTOR inhibitor rapamycin both reduced the metabolic activity and proliferation of NK cells and reduced the abundances of v..

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Awarded by European Research Council

Awarded by National Health and Medical Research Council (NHMRC) of Senior Principal Research Fellowship

Funding Acknowledgements

The T.W. laboratory is supported by the Agence Nationale de la Recherche, European Research Council (ERC-Stg 281025), INSERM, CNRS, Universite de Lyon, and ENS de Lyon. M.J.S. is supported by a National Health and Medical Research Council (NHMRC) of Senior Principal Research Fellowship (1078671) and Program grant (1013667). F.S.-F.G. is supported by a National Breast Cancer Foundation, an NHMRC Early Career Fellowship, and a Cure Cancer Australia Priority-Driven Young Investigator Project Grant.