Braza, Mounia SGarcia, MercedesBrahmachary, ManishaPothula, VenuFay, FrancoisBoros, PeterWerner, Sherry AGinhoux, FlorentMulder, Willem J MOchando, JordiConde-San Román, PatriciaCortegano, Isabel2020-06-152020-06-152018Am J Transplant . 2018 May;18(5):1247-1255.http://hdl.handle.net/20.500.12105/10395The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance. These results provide new mechanistic insights into the developmental requirements of tolerogenic macrophages and identify CSF1 producing neutrophils as critical regulators of the immunological response.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/Heart TransplantationAnimalsCell DifferentiationCell ProliferationFemaleHumansImmune ToleranceMacrophage Colony-Stimulating FactorMacrophagesMaleMiceMice, Inbred BALB CMice, Inbred C57BLNeutrophilsSignal TransductionTransplantation ToleranceAtribución-NoComercial-CompartirIgual 4.0 Internacional293145581851247-125510.1111/ajt.146451600-6143American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeonsopen access