Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

Mounia S. Braza, Patricia Conde, Mercedes Garcia, Isabel Cortegano, Manisha Brahmachary, Venu Pothula, Francois Fay, Peter Boros, Sherry A. Werner, Florent Ginhoux, Willem J.M. Mulder, Jordi Ochando

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1247-1255
Number of pages9
JournalAmerican Journal of Transplantation
Issue number5
StatePublished - May 2018


  • basic (laboratory) research/science
  • immunobiology
  • macrophage/monocyte biology: differentiation/maturation
  • tolerance: mechanisms

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


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