Chemokine Gene Silencing in Decidual Stromal Cells Limits T Cell Access to the Maternal-Fetal Interface

Keeping Baby Safe Because half the genes from a developing fetus are inherited from the father, from the mother's perspective, a fetus is “foreign.” How, then, does the maternal immune system tolerate the fetus? Nancy et al. (p. 1317) found that careful regulation of cellular recruitment signals allowed for fetal tolerance in mice. Although high numbers of T cells localized to the myometrium layer of the uterine wall in pregnant mice, very few T cells were found in the decidua, the uterine tissue that encapsulates the fetus and placenta. Thus, in pregnancy, regulation of immune cell localization may allow for organ-specific immune tolerance. Turning off the expression in the placenta of T cell attractants allows the mother to tolerate the fetus. The chemokine-mediated recruitment of effector T cells to sites of inflammation is a central feature of the immune response. The extent to which chemokine expression levels are limited by the intrinsic developmental characteristics of a tissue has remained unexplored. We show in mice that effector T cells cannot accumulate within the decidua, the specialized stromal tissue encapsulating the fetus and placenta. Impaired accumulation was in part attributable to the epigenetic silencing of key T cell–attracting inflammatory chemokine genes in decidual stromal cells, as evidenced by promoter accrual of repressive histone marks. These findings give insight into mechanisms of fetomaternal immune tolerance, as well as reveal the epigenetic modification of tissue stromal cells as a modality for limiting effector T cell trafficking.