Antigen‐Presenting Cells and Materno‐Fetal Tolerance: An Emerging Role for Dendritic Cells

Abstract

During pregnancy, a delicate balance of innate and adaptive immune responses at the maternal-fetal interface promotes survival of the semi-allogeneic embryo and, at the same time, allows effective immunity to protect the mother from environmental pathogens. As in other tissues, antigen handling and processing in the decidualized endometrium constitutes a primary event in the onset of immune responses and is therefore likely to determine their stimulatory or tolerogenic nature. Maternal antigen-presenting cells [macrophages and dendritic cells (DCs)] are scattered throughout the decidualized endometrium during all stages of pregnancy and appear to be important players in this feto-maternal immune adjustment. This review focuses on the characterization of decidual macrophages and DCs, as well as their involvement in cell-cell interactions within the decidual leukocyte network, which are likely to influence uterine and placental homeostasis as well as the local maternal immune responses to the fetus during pregnancy.

Depletion of Invariant NKT Cells Reduces Inflammation-Induced Preterm Delivery in Mice

“…Depletion of DCs has been shown to prevent blastocyst implantation and decidua formation, suggesting that uterine DCs are necessary for decidualization and affect the angiogenic response by inhibiting blood vessel maturation (29). Additionally, recent evidence points to a pivotal role of DCs in shaping the cytokine profile toward the establishment of a tolerogenic microenvironment at the maternal/fetal interface (30). Although DCs contribute to an immunosuppressive atmosphere over the course of gestation, they possess the capacity to contribute to proinflammatory responses upon pathogenic activation.…”

Immunological role of vitamin D at the maternal–fetal interface

“…First-trimester human CD83 C decidual DCs possess T cell immune-stimulatory capacity in ex vivo mixed leukocyte reactions and also cluster with T cells in situ (Kammerer et al 2000). Decidual DCs appear to be more tolerogenic than their peripheral blood counterparts, with a lower capacity for antigen presentation, reduced expression of co-stimulatory molecules, reduced expression of inflammatory cytokines such as IL12 and enhanced expression of anti-inflammatory cytokines such as IL10 (Laskarin et al 2007, Arck et al 2013. This is consistent with an immature DC phenotype that is generally associated with a more tolerogenic T-cell response (Kammerer et al 2003).…”

“…Monocytes can also differentiate into DCs (CD83 C ), which populate the decidua throughout pregnancy (Laskarin et al 2007). In human decidua, DCs are relatively sparse compared with macrophages (w1% of total decidual cells (Kammerer et al 2000)), questioning the functional importance of these cells in the decidua (Rieger et al 2004).…”

Vitamin D and Human Pregnancy

“…Instead, the presence of VDR in the placenta has highlighted potential autocrine or paracrine functions for vitamin D at the fetal-maternal interface 109 . One possible explanation is that 1,25(OH) 2 D acts as a locally synthesized regulator of placental calcium transport 109 , but an immunmodulatory function has also been proposed 110 114,115 immunity, and thus it is possible that vitamin D will exert effects on a variety of responses during pregnancy, including implantation, as well as responses to infection and inflammation. Indeed, expression of VDR and CYP27B1 has been reported in many tissues that can be broadly termed 'barrier sites' 116,117 , indicating that localized responses to vitamin D may be a key feature of these tissues.…”