Innate Lymphoid Cells in the Maternal and Fetal Compartments

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.

Innate Immune Responses to Acute Viral Infection During Pregnancy

“…On this basis, ILC have been described as "innate counterparts" of T cells (151). Their abundance at the maternal-fetal interface suggests pivotal roles in both innate immune defense and normal placental development (152). Table 2 summarizes the classification and functions of decidual ILC: Given the recent discovery of ILC, data on their antiviral properties are still accumulating.…”

Cellular immune responses in amniotic fluid of women with preterm prelabor rupture of membranes

“…Amniotic fluid contains a diverse array of innate and adaptive immune cells that vary as normal gestation progresses [49]. Specifically, neutrophils, monocytes/macrophages, T cells, innate lymphoid cells, natural killer (NK) cells, and B cells are present in the amniotic cavity of women with a normal pregnancy [49][50][51]. These cellular immune responses are augmented in women with pregnancy complications such as preterm labor with intact membranes [52], clinical chorioamnionitis at term [53], and preterm clinical chorioamnionitis [54].…”

Are B cells altered in the decidua of women with preterm or term labor?

“…To date, the most studied causes of pathological inflammation leading to preterm labor have been (a) intra‐amniotic infection/inflammation resulting from microbial invasion of the amniotic cavity and (b) intra‐amniotic inflammation without detectable microorganisms (ie, sterile intra‐amniotic inflammation) identified by using both molecular and conventional microbiological techniques, proposed to be due to endogenous danger signals, or alarmins . Most research concerning inflammation‐induced preterm labor has therefore focused on the innate limb of immunity . Yet, several studies reported strong evidence that T cells, the primary cellular component of the adaptive immune system, are present at the maternal‐fetal interface .…”