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

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 various NK cell…

• NB
  National Breast Cancer Foundation
• CC
  Cure Cancer Australia Foundation
• AN
  Agence Nationale de la Recherche
• IN
  Institut National de la Santé et de la Recherche Médicale
• CN
  Centre National de la Recherche Scientifique
• ER
  European Research Council

  Award: ERC-Stg 281025
• NH
  National Health and Medical Research Council

  Awards: 1013667, 1078671