Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance.

The 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 co...

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Detalles Bibliográficos
Autores: Braza, Mounia S, Garcia, Mercedes, Brahmachary, Manisha, Pothula, Venu, Fay, Francois, Boros, Peter, Werner, Sherry A, Ginhoux, Florent, Mulder, Willem J M, Ochando, Jordi, Conde-San Román, Patricia, Cortegano, Isabel
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10395
Acceso en línea:http://hdl.handle.net/20.500.12105/10395
Access Level:acceso abierto
Palabra clave:Heart Transplantation
Animals
Cell Differentiation
Cell Proliferation
Female
Humans
Immune Tolerance
Macrophage Colony-Stimulating Factor
Macrophages
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neutrophils
Signal Transduction
Transplantation Tolerance
Descripción
Sumario:The 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.