The Balance between Conventional DCs and Plasmacytoid DCs Is Pivotal for Immunological Tolerance during Pregnancy in the Mouse.
The Balance between Conventional DCs and Plasmacytoid DCs Is Pivotal for Immunological Tolerance during Pregnancy in the Mouse.
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常规 DC 和浆细胞样 DC 之间的平衡对于小鼠妊娠期间的免疫耐受至关重要
DOI：
10.1038/srep26984
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发表时间：
2016-05-27
影响因子：
4.6
通讯作者：
Peng JP
中科院分区：
文献类型：
--
作者：
Fang WN;Shi M;Meng CY;Li DD;Peng JP
树突状细胞（DC）可以根据微环境塑造其功能，对于怀孕期间免疫和耐受的微妙平衡至关重要。然而，在怀孕期间DC分化的微环境教育的可塑性的机制在很大程度上仍然不清楚。在这里，我们发现，传统的DC（cDC）和浆细胞样DC（pDC）的分化在怀孕期间以组织特异性的方式进行调节。cDC和pDC的比例在脾脏中保持恒定。然而，该比率在主动脉旁淋巴结（LN）中发生变化，其中cDC百分比显著降低，同时pDC从E8.5增加至E16.5。此外，pDC和调节性T细胞（Treg）的扩增在主动脉旁LN中相关，并且与cDC相比，pDC具有更大的诱导调节性T细胞（Treg）的潜力（独立于IDO表达）。值得注意的是，cDC和pDC之间的平衡在IFN-γ诱导的异常妊娠中被破坏，伴随着主动脉旁LN和蜕膜中较低的Treg百分比。为了进一步确定潜在的机制，我们发现升高的IFN-γ可以增加GM-CSF的水平以改变pDC在体内向cDC的分化。因此，我们提供了一种新的调节机制，妊娠相关的免疫耐受，涉及DC亚群的平衡，这可能提供了一个新的目标，为预防人类自然流产。
Dendritic cells (DCs), which can shape their functions depending on the microenvironment, are crucial for the delicate balance of immunity and tolerance during pregnancy. However, the mechanism underlying the microenvironment-educated plasticity of DC differentiation during pregnancy remains largely unclear. Here, we found that the differentiation of conventional DCs (cDCs) and plasmacytoid DCs (pDCs) is regulated in a tissue-specific manner during pregnancy. The ratio of cDCs and pDCs remained constant in the spleen. However, the ratio changed in the para-aortic lymph nodes (LNs), where cDC percentages were significantly reduced concurrent with an increase in pDCs from E8.5 to E16.5. Moreover, the expansion of pDCs and T regulatory (Treg) cells was correlated in the para-aortic LNs, and pDCs had more potential to induce regulatory T cells (Tregs) compared with cDCs (independent of IDO expression). Notably, the balance between cDCs and pDCs is disrupted in IFN-γ-induced abnormal pregnancy, accompanied by lower Treg percentages in the para-aortic LNs and decidua. To further identify the underlying mechanism, we found that elevated IFN-γ can increase the levels of GM-CSF to alter the differentiation of pDCs into cDCs in vivo. Therefore, we provide a novel regulatory mechanism underlying pregnancy-related immune tolerance that involves the balance of DC subsets, which may offer a new target for the prevention of human spontaneous abortion.