Macrophages at the Fetal-Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10
Macrophages at the Fetal-Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10
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DOI：
10.4049/jimmunol.1100130
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发表时间：
2011-10-01
影响因子：
4.4
通讯作者：
Ernerudh, Jan
中科院分区：
文献类型：
--
作者：
Svensson, Judit;Jenmalm, Maria C.;Ernerudh, Jan
在怀孕期间，母体免疫系统会受到胎儿的存在的挑战，尽管是半同种异体，但必须耐受胎儿的存在。子宫粘膜（或蜕膜）巨噬细胞（M phi）是胎儿-母体界面的主要白细胞群之一，与胎儿耐受性有关，但有关其调节的信息很少。在这项研究中，我们通过体外 M phi 分化模型研究了可能参与蜕膜 M phi 分化和极化的几个因素的作用。通过使用流式细胞术，我们表明 M-CSF 和 IL-10 是人蜕膜 M phi 上表达的 M2（免疫调节）M phi 标记物（CD14、CD163、CD206、CD209）的有效诱导剂。相反，促炎刺激以及与Th2相关的IL-4和IL-13出人意料地诱导了不同的表达模式，表明Th2主导的环境对于蜕膜M phi极化来说不是必需的。 M-CSF/IL-10 刺激和蜕膜 M phi 也显示出相似的细胞因子分泌模式，产生 IL-10 以及 IL-6、TNF 和 CCL4。相反，促炎性LPS/IFN-γ刺激的M phi 产生显着更高水平的TNF，但不产生IL-10。我们还使用了包含 420 M phi 相关基因的基因阵列，其中 100 个先前报道在蜕膜 M phi 的全局基因表达谱中受到调节，证实 M-CSF/IL-10 诱导的 M phi 与蜕膜 M phi 密切相关。总而言之，我们的结果一致表明 M-CSF，特别是 IL-10 在形成具有调节特性的蜕膜 M phi 中发挥着核心作用。因此，这些细胞因子可能在支持成功妊娠所需的稳态和耐受免疫环境方面发挥重要作用。免疫学杂志，2011，187：3671-3682。
During pregnancy, the maternal immune system is challenged by the presence of the fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or decidual) macrophages (M phi), one of the major leukocyte populations at the fetal-maternal interface, have been implicated in fetal tolerance, but information regarding their regulation is scarce. In this study, we investigated the role of several factors potentially involved in the differentiation and polarization of decidual M phi with an in vitro M phi differentiation model. By using flow cytometry, we showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) M phi markers expressed on human decidual M phi (CD14, CD163, CD206, CD209). In contrast, proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13, induced different patterns of expression, indicating that a Th2-dominated environment is not required for decidual M phi polarization. M-CSF/IL-10-stimulated and decidual M phi also showed similar cytokine secretion patterns, with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN-gamma-stimulated M phi produced significantly higher levels of TNF and no IL-10. We also used a gene array with 420 M phi-related genes, of which 100 were previously reported to be regulated in a global gene expression profiling of decidual M phi, confirming that M-CSF/IL-10-induced M phi are closely related to decidual M phi. Taken together, our results consistently point to a central role for M-CSF and in particular IL-10 in the shaping of decidual M phi with regulatory properties. These cytokines may therefore play an important role in supporting the homeostatic and tolerant immune milieu required for a successful pregnancy. The Journal of Immunology, 2011, 187: 3671-3682.