Dendritic cells: a family portrait at mid‐gestation

Abstract

Summary Recent advances in our understanding of dendritic cells (DCs) and their role in tolerance and immunity has fuelled study of their normal development and function within the reproductive tract. The common hypothesis that pregnancy is a state of immune suppression or deviation now includes the idea that alterations in DC phenotype and function are critical for maternal tolerance. We chose to study DCs in the uterus and lymphoid tissue in non‐pregnant and pregnant mice at mid‐gestation to understand what DC‐related factors may be involved in premature birth. We used a mouse model where the mother’s immune system has been shown to respond to the male antigen H‐Y. Observed differences among DCs in the uterus, uterine draining nodes and spleen, even in non‐pregnant mice, suggest the existence of a specialized uterus‐specific subset of DCs. We further found that, amongst CD45+ CD11c+ cells in the uterus and peripheral lymphoid tissue of pregnant mice, expression of major histocompatibility complex class II (MHC II) and costimulatory molecules (i.e. CD80) was similar to that in the non‐pregnant state. Moreover, there was no pregnancy‐related decrease in the proportion of CD11c+ cells in the uterus or in the uterine node that were CD11b− CD8+. Pregnancy increased the CD11b+ subsets and the expression of chemokine (C‐C motif) ligand 6 (CCL6) in DCs of the uterine draining nodes. Finally, DC subsets showed variable expression, with respect to tissue and pregnancy, of the cytokine interleukin‐15, which is important in lymphoid cell homeostasis. For DCs, pregnancy is not a state of immune paralysis, but of dynamic developmental change.

Chronic inflammatory lesions of the placenta are associated with an up-regulation of amniotic fluid CXCR3: A marker of allograft rejection

“…During pregnancy, maternal T cells recognize fetal antigens through interactions with antigen-presenting cells [122,123]. Fetal antigen-specific Tregs (regulatory T cells) maintain maternal-fetal tolerance throughout pregnancy [3,4,124].…”

Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats

“…The cytokine CCL6 is a chemoattractant for helper T cells, B cells, and macrophages (Bizargity & Bonney, 2009). Additionally, CCL6 may play an important role in early brain development by attracting primitive macrophages and microglia into the developing brain (Bilbo & Schwarz, 2012).…”

Immune Regulation in Pregnancy

“…The result of this interaction can result in activation and proliferation of T cells specific for the protein whose peptide is in the MHC molecule. The dendritic cell population is likely to be slightly different depending on the tissue of residence, and this is true with regard to the placenta, uterus, uterine draining node and spleen 56 . It is possible that tissue-specific differences in the dendritic cell population are developmentally regulated.…”

“…Other possibilities of control of dendritic cell function may occur at the level of maturation 58, 59 , as it has been proposed that “immature” dendritic cells support immune tolerance of tissue grafts 60 and cancers 61 . However, inflammation can override these mechanisms and produce activation of dendritic cells from the uterus 56 .…”