Inviting regulatory T cells to pregnant endometrium: friends or foes in adverse pregnancy outcomes?

Among decidual immune cells, regulatory T cells (Tregs) have been unanimously recognized as central contributors to tolerance and maintenance of healthy pregnancy. Numerical and functional downregulation of Tregs or disturbed interaction of Tregs with trophoblasts and other immune cells have been linked to early pregnancy loss such as idiopathic infertility and miscarriage and later-onset adverse pregnancy outcomes including preeclampsia. This review focuses on the mechanisms for regulating the generation, expansion, and function of Tregs, the roles of Tregs in maintaining maternal immune tolerance through crosstalk with trophoblasts and other decidual regulatory immune cells, and how Tregs may play foes to pregnancy and contribute to the programming of pregnancy-related complications. Therapeutic options for implantation failure and adverse pregnancy outcomes are now part of the emerging significance of Tregs in pregnancy tolerance and maintenance.