Immune-Metabolic Interactions and T Cell Tolerance in Pregnancy

Pregnancy depends on a state of maternal immune toler-ance mediated by CD4+ regulatory T (Treg) cells. Uterine Treg cells release anti-inflammatory factors, inhibit effector immunity, and support adaptation of the uterine vascula-ture to facilitate placental development. Insufficient Treg cells or inadequate functional competence is implicated in infertility and recurrent miscarriage, as well as pregnancy complications preeclampsia, fetal growth restriction, and preterm birth, which stem from placental insufficiency. In this review we address an emerging area of interest in preg-nancy immunology -the significance of metabolic status in regulating the Treg cell expansion required for maternal -fetal tolerance. We describe how hyperglycemia and insulin resistance affect T cell responses to suppress generation of Treg cells, summarize data that implicate a role for altered glucose metabolism in impaired maternal -fetal tolerance, and explore the prospect of targeting dysregulated meta-bolism to rebalance the adaptive immune response in women experiencing reproductive disorders. The Journal ofImmunology, 2022, 209: 1426-1436.

Automated summary

Pregnancy depends on maternal immune tolerance mediated by regulatory T cells. The metabolic status plays an important role in regulating the expansion of these T cells. Metabolic abnormalities can lead to insufficient regulatory T cells and contribute to infertility, recurrent miscarriage, and pregnancy complications.