Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance.

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance.
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DOI:
10.1111/ajt.14645
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发表时间:
2018-05
期刊:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子:
--
通讯作者:
Ochando J
Ochando J
中科院分区:
其他
文献类型:
--
作者:
Braza MS;Conde P;Garcia M;Cortegano I;Brahmachary M;Pothula V;Fay F;Boros P;Werner SA;Ginhoux F;Mulder WJM;Ochando J

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殖民地刺激因子1(CSF 1)调节组织巨噬细胞的分化和功能,并决定免疫应答的结果。CSF1介导的巨噬细胞发育背后的分子机制仍有待阐明。在这里,我们证明了中性粒细胞衍生的CSF 1控制巨噬细胞极化和增殖,这是诱导耐受所必需的。使用载有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CSF 1或防止巨噬细胞增殖,消除了耐受性的诱导。这些结果为致耐受性巨噬细胞的发育要求提供了新的机制见解,并将产生CSF 1的中性粒细胞鉴定为免疫应答的关键调节剂。在这篇文章中,Ochando及其同事证明了移植物浸润中性粒细胞产生CSF 1,促进巨噬细胞极化并介导接受共刺激阻断治疗的受体小鼠的移植耐受。
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.
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