Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance

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

来源：American Journal of Transplantation, 2018, 18(5): 1247-1255.

DOI：10.1111/ajt.14645

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

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.
In this article, Ochando and colleagues demonstrate that graft-infiltrating neutrophils produce CSF1 that promotes macrophage polarization and mediates transplantation tolerance in recipient mice treated with costimulation blockade.

• 出版日期2018-5