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Review
. 2018 Oct 26;9:2396.
doi: 10.3389/fimmu.2018.02396. eCollection 2018.

Innate Lymphoid Cells in the Maternal and Fetal Compartments

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Free PMC article
Review

Innate Lymphoid Cells in the Maternal and Fetal Compartments

Derek Miller et al. Front Immunol. .
Free PMC article

Abstract

Pregnancy success is orchestrated by the complex balance between the maternal and fetal immune systems. Herein, we summarize the potential role of innate lymphoid cells (ILCs) in the maternal and fetal compartments. We reviewed published literature describing different ILC subsets [ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells] in the uterus, decidua, fetal tissues [liver, secondary lymphoid organs (SLO), intestine, and lung] and amniotic cavity. ILC1s, ILC2s, and ILC3s are present in the murine uterus prior to and during pregnancy but have only been detected in the non-pregnant endometrium in humans. Specifically, ILC2s reside in the murine uterus from mid-pregnancy to term, ILC1s increase throughout gestation, and ILC3s remain constant. Yet, LTi cells have only been detected in the non-pregnant murine uterus. In the human decidua, ILC1s, ILC3s, and LTi-like cells are more abundant during early gestation, whereas ILC2s increase at the end of pregnancy. Decidual ILC1s were also detected during mid-gestation in mice. Interestingly, functional decidual ILC2s and ILC3s increased in women who underwent spontaneous preterm labor, indicating the involvement of such cells in this pregnancy complication. Fetal ILCs exist in the liver, SLO, intestine, lung, and amniotic cavity. The fetal liver is thought to be the source of ILC progenitors since the differentiation of these cells from hematopoietic stem cells occurs at this site, and mature ILC subsets can be found in this compartment as well. The interaction between LTi cells and specialized stromal cells is important during the formation of SLO. Mature ILCs are found at the mucosal surfaces of the lung and intestine, from where they can extravasate into the amniotic cavity. Amniotic fluid ILCs express high levels of RORγt, CD161, and CD103, hallmarks of ILC3s. Such cells are more abundant in the second trimester than later in gestation. Although amniotic fluid ILC3s produce IL-17A and TNFα, indicating their functionality, their numbers in patients with intra-amniotic infection/inflammation remain unchanged compared to those without this pregnancy complication. Collectively, these findings suggest that maternal (uterine and decidual) ILCs play central roles in both the initiation and maintenance of pregnancy, and fetal ILCs participate in the development of immunity.

Keywords: LTi; amniotic cavity; decidua; maternal-fetal interface; neonate; pregnancy; preterm labor; uterus.

Figures

Figure 1
Figure 1
Innate lymphoid cells in the uterus and decidua. (A) ILC1s, ILC2s, and ILC3s are present in the murine uterus prior to and during pregnancy, but have only been detected in the non-pregnant endometrium in humans. ILC2s reside in the murine uterus from mid-pregnancy to term, whereas ILC1s increase throughout gestation and ILC3s remain constant. However, lymphoid tissue inducer (LTi) cells have only been detected in the non-pregnant murine uterus. Further studies are needed to confirm the presence and functions of uterine ILCs during human pregnancy. (B) In the human decidua, ILC1s, ILC3s, and LTi-like cells are more abundant during early gestation, whereas ILC2s are increased at the end of pregnancy. Decidual ILC1s were also detected during mid-gestation in mice. Interestingly, functional decidual ILC2s and ILC3s are increased in women who underwent spontaneous preterm labor (PTL), indicating the involvement of such cells in this pregnancy complication.
Figure 2
Figure 2
Fetal innate lymphoid cells. Fetal ILCs exist in the liver, secondary lymphoid organs (SLO), intestine, lung, and amniotic cavity. The fetal liver is thought to be the source of ILC progenitors (ILCP) since the differentiation of these cells from hematopoietic stem cells (HSC) occurs at this site, and mature ILC subsets can be found in this compartment as well. The interaction between lymphoid tissue inducer (LTi) cells and specialized stromal cells is important during the formation of SLO. Mature ILCs are found at the mucosal surfaces of the lung and intestine, from where they can extravasate into the amniotic cavity. These findings support a role for ILCs as central regulators in fetal development and immunity.
Figure 3
Figure 3
Innate lymphoid cells in the amniotic cavity. Functional ILC3s are found in the mucosal epithelium of fetal tissues such as the intestines, from where they may extravasate into the amniotic cavity. Amniotic fluid ILCs reach their highest proportions during the second trimester, yet are still present at the end of gestation.

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