Previousstudies in mice identified

Previous
studies in mice identified a population of immature NK
cells with phenotypic and functional features typical of regulatory cells (Ebata et al., 2006). In addition, these cells
were abundant at the feto–maternal interface where they
may play a substantial role in the maintenance of pregnancy (Lin et al., 2009). On the other hand, studies in
humans revealed the presence of Tregs both in PB and
in decidua during the early phases of normal pregnancies
(Heikkinen et al., 2004; Saito et al., 2010). In some cases,
spontaneous abortions have been associated with low Treg
cell proportions in PB (Sasaki et al., 2004; Saito, 2010).
Remarkably, in tumors, it has been shown that Treg cells
generate a tolerant microenvironment as a result of the
interaction with other cell types, including myelomonocytic cells (Rabinovich et al., 2007). A similar mechanism
could take also place in decidual tissues during early pregnancy (Barrientos et al., 2009). In this context, however, it
was unclear how Tregs could be induced. A possible explanation was that Tregs could be induced by indoleamine
2,3-dioxygenase (IDO) and/or other suppressive mechanisms, possibly involving the particular CD14
+
myeloid
cells present in the decidua (Munn et al., 1998; Fallarino
et al., 2003; Terness et al., 2007).
Notably, previous studies in mice revealed that IDO
is expressed by myeloid cells in decidua and that IDO
inhibitors can cause miscarriages, suggesting a key role
in the maintenance of pregnancy and in the induction
of Tregs. Remarkably, dCD14
+
cells display phenotypic
characteristics typical of polarized M2 macrophages or
of immature dendritic cells (DCs) (Bulmer and Johnson,
1984; Blois et al., 2007; Laskarin et al., 2008). Histochemical analysis revealed that dNK cells can reside in
close association with dCD14
+
cells, a condition that could
result in functional cross-talk between the two cell types
(Kammerer et al., 2003). Indeed, we showed that the
interaction between dNK cells and dCD14
+
cells promotes
the induction of Tregs characterized by the CD25
bright
and FOXP3
+
phenotype. Upon interaction with dCD14
+
cells, dNK cells release IFN. In turn, IFN induces the
expression of IDO in dCD14
+
cells. The IDO metabolite
l-kynurenine, does not affect IFN production by dNK
cells (thus differing from PB NK cells). Other mechanisms are involved in Treg induction by dCD14
+
cells,
including the release of TGF and the expression of CTLA-4, which interacts with its ligand expressed by T cells
(Vacca et al., 2010). Thus, the cross-talk between decidual NK and CD14
+
cells may initiate a process leading
to Treg induction and immunosuppression. Remarkably,
previous studies reported a marked reduction of dNK
cells in cases of spontaneous abortion during the first
trimester. Taken together, these studies support the notion
that, in decidual tissues, NK cells might play an important role in modulating maternal immune responses and
in tolerance induction (Karimi and Arck, 2010). Moreover, they provide new insight into the immunoregulatory
events occurring at the maternal–fetal interface resulting
from cellular interactions among dCD14
+
, dNK, and Treg
cells.

結果 (中文) 3:

以前的研究发现在小鼠
人口
未成熟NK细胞的表型和功能特征典型的调节性T细胞（ebata等人。，2006）。此外，这些细胞
丰富在胎儿–母胎界面里
可能妊娠的维持中发挥重要作用（Lin等人。，2009）。另一方面，研究人类发现的铅和
正常妊娠蜕膜中
早期调节性T细胞的存在（哈基宁等人。，2004；Saito等人。，2010）。在某些情况下，
流产已与Treg细胞比例
铅低相关（Sasaki等人。，2004；Saito，2010）。
明显，肿瘤，它已经表明，Treg细胞
生成一个宽容的环境由于与其他细胞类型的
互动，包括单核细胞（Rabinovich等人。，2007）。一个类似的机制
可以也发生在妊娠早期蜕膜组织（巴里恩托斯等人。，2009）。然而在这种情况下，它是不清楚，
Tregs可诱导。一个可能的解释是，调节性T细胞可以通过吲哚胺2,3-双加氧酶的诱导
（IDO）和/或其他抑制机制，可能涉及特定的CD14

髓
细胞在蜕膜（芒恩等人。，1998；Fallarino
等人。，2003；冬等人。，2007）。
值得注意的是，在小鼠的研究表明，我
的髓系细胞和蜕膜组织，
表达IDO抑制剂可引起流产，建议在妊娠的维持和调节性T细胞的诱导
关键作用
。值得注意的是，dcd14

细胞表型特征显示
M2巨噬细胞或
未成熟树突状细胞（DCs）（Bulmer和约翰逊，
1984；布卢瓦等人。，2007；laskarin等人。，2008）。组织化学分析表明，dNK细胞可以驻留在
密切的联系dcd14

细胞，条件是可以
在两种类型的细胞
功能之间的串扰结果（卡默莱昂等人。，2003）。事实上，我们发现，
互动和dcd14 dNK细胞

细胞促进
诱导Treg细胞的特征
亮
和
CD25 Foxp3
表型。在互动dcd14

细胞，dNK细胞释放干扰素。反过来，诱导干扰素的
表达IDO在dcd14

细胞。IDO代谢物
犬尿氨酸，不影响 DNK
细胞干扰素生产（因而不同于PB NK细胞）。其他机制参与调节性T细胞的诱导dcd14

细胞，
包括释放TGF- 和CTLA-4的表达，这与它的配体表达的T细胞
（瓦卡等人。，2010）。因此，之间的串扰蜕膜NK和CD14

细胞会启动一个进程的主导
Treg诱导免疫抑制。值得注意的是，
以前的研究报告显着减少蜕膜细胞
自然流产的情况下，第一
孕期。总之，这些研究支持了这一观点
，蜕膜组织，NK细胞可能在免疫耐受的诱导调节母体的免疫反应和
发挥重要作用（2010公司和芳环细胞分裂素，）。此外，他们提供新的洞察的免疫调节
事件发生在母体–母胎界面细胞之间的相互作用产生的
dcd14

，DNK，Treg细胞和
。