Faculty Publication: Placental regulation

Arianna Smith, Assistant Professor Biology, has published the chapter, “Placental regulation of immune functions” in the book Reproductive Immunology with co-authors Paulomi Bole Aldo and Karen E. Racicot.


The placenta is a highly specialized organ that serves as the primary interface between the maternal environment and the fetus. One important placental function is to promote the development of maternal immune phenotypes that will prevent detrimental immune activation in response to paternal antigens. For example, trophoblast-derived cytokines promote the development of “M2” or tissue-repair phenotypes in decidual macrophages, which are less likely to become activated and gain pro-inflammatory phenotypes. Trophoblast cells can inhibit NK cell activation by secreting soluble or exosome-associated ligands for NK cell inhibitory receptors. T-lymphocytes are also influenced by placental paracrine factors, some of which promote regulatory and anti-inflammatory T-cell polarization and others that induce apoptosis in T-cells with pro-inflammatory phenotypes. Therefore, the placenta helps to shape a very unique maternal immune environment that is both supportive and protective of pregnancy. But, not only does the placenta regulate maternal immune functions, but it can also affect the development and maturation of the fetal immune system. A key regulator of fetal growth and programming, the placenta secretes immune factors that enter fetal circulation where they are proposed to influence fetal immune development. The fetal immune system is also sensitive to in utero programming by environmental exposures, such as maternal stress and inflammation, which are linked to increased risk for immune-related diseases in offspring. While we are only beginning to understand the mechanisms underlying the links between these exposures and postnatal immune outcomes, the placenta is likely to play an important role. In this chapter, we will examine how the placenta regulates both maternal and fetal immune systems to support pregnancy and fetal development.

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