IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ.
IL-34 induces the differentiation of human monocytes into immunosuppressive macrophages. antagonistic effects of GM-CSF and IFNγ.
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DOI：
10.1371/journal.pone.0056045
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jeannin P
中科院分区：
文献类型：
--
作者：
Foucher ED;Blanchard S;Preisser L;Garo E;Ifrah N;Guardiola P;Delneste Y;Jeannin P
IL-34是最近鉴定的细胞因子，其通过M-CSF受体发出信号并促进单核细胞存活。取决于环境，单核细胞可以分化成巨噬细胞（Mφ）或树突状细胞（DC）。Mφ和DC亚群具有广泛的表型和功能。迄今为止，暴露于IL-34的单核细胞的表型仍未探索。我们在此报告IL-34诱导单核细胞分化为CD 14 high CD 163 high CD 1a − Mφ（IL-34-Mφ）。在LPS刺激下，IL-34-Mφ表现出IL-10高、IL-12低、M2低的特性，并表达低水平的共刺激分子CD 80和CD 86。IL-34-Mφ表现出较差的T细胞共刺激特性，并且具有有效的免疫抑制特性（减少TCR刺激的T细胞增殖）。对于分析的所有参数，IL-34-Mφ在表型和功能上与M-CSF-Mφ相似。IL-34在诱导免疫抑制性Mφ的产生方面与M-CSF一样有效。此外，IL-34-Mφ的产生是通过M-CSF受体介导的，不依赖于内源性M-CSF消耗，并由IL-6增强。在试图确定防止在某些病理情况下有害的M2细胞积聚的策略时，我们观察到IFNγ和GM-CSF防止由IL-34诱导的免疫抑制性Mφ的产生。IFNγ还将已建立的IL-34-Mφ转换为免疫刺激性Mφ。总之，我们证明了IL-34以类似于M-CSF的方式驱动单核细胞分化为免疫抑制性M2，并且IFNγ和GM-CSF阻止了这种作用。
IL-34 is a recently identified cytokine that signals via the M-CSF receptor and promotes monocyte survival. Depending on the environment, monocytes can differentiate into macrophages (Mφ) or dendritic cells (DC). A wide spectrum of Mφ and DC subsets, with distinct phenotypes and functions, has been described. To date, the phenotype of monocytes exposed to IL-34 remains unexplored. We report here that IL-34 induces the differentiation of monocytes into CD14high CD163high CD1a− Mφ (IL-34-Mφ). Upon LPS stimulation, IL-34-Mφ exhibit an IL-10high IL-12low M2 profile and express low levels of the costimulatory molecules CD80 and CD86. IL-34-Mφ exhibit poor T cell costimulatory properties, and have potent immunosuppressive properties (decrease of TCR-stimulated T cell proliferation). For all the parameters analyzed, IL-34-Mφ are phenotypically and functionally similar to M-CSF-Mφ. IL-34 appears as efficient as M-CSF in inducing the generation of immunosuppressive Mφ. Moreover, the generation of IL-34-Mφ is mediated through the M-CSF receptor, is independent of endogenous M-CSF consumption and is potentiated by IL-6. In an attempt to identify strategies to prevent a deleterious M2 cell accumulation in some pathological situations, we observed that IFNγ and GM-CSF prevent the generation of immunosuppressive Mφ induced by IL-34. IFNγ also switches established IL-34-Mφ into immunostimulatory Mφ. In conclusion, we demonstrate that IL-34 drives the differentiation of monocytes into immunosuppressive M2, in a manner similar to M-CSF, and that IFNγ and GM-CSF prevent this effect.
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