Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Immunología de Transplantes, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Am J Transplant. 2018 May;18(5):1247-1255. doi: 10.1111/ajt.14645. Epub 2018 Feb 7.
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.
集落刺激因子 1（CSF1）调节组织巨噬细胞的分化和功能，并决定免疫反应的结果。CSF1 介导的巨噬细胞发育的分子机制仍有待阐明。本文中，作者证明了中性粒细胞衍生的 CSF1 控制巨噬细胞的极化和增殖，这对于诱导耐受是必要的。使用负载细胞周期抑制剂辛伐他汀的靶向纳米颗粒抑制中性粒细胞产生 CSF1 或阻止巨噬细胞增殖，会破坏耐受的诱导。这些结果为诱导耐受的巨噬细胞的发育要求提供了新的机制见解，并确定产生 CSF1 的中性粒细胞是免疫反应的关键调节因子。
