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Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance |
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| Authors: | 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 |
| Affiliation: | 1. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;2. Immunología de Transplantes, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain;3. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;4. Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA;5. Health Science Center, University of Texas, San Antonio, TX, USA;6. Singapore Immunology Network, Agency for Science, Technology and Research (A?STAR), Singapore, Singapore |
| Abstract: | 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. |
| Keywords: | basic (laboratory) research/science immunobiology macrophage/monocyte biology: differentiation/maturation tolerance: mechanisms |