Pregnancy establishment and maintenance represents a challenge for the maternal immune system. It has to be alert against pathogens while tolerating paternal alloantigens in fetal structures. The maternal immune system is not only aware of these alloantigens, but it also actively tolerates them to ensure the survival of the fetus throughout pregnancy. Regulatory T cells (Treg) are reportedly involved in this process. They are known to act in both paracrine and cell-contact dependent ways and therefore their cellular localization is essential for their functional ability of suppressing specific immune responses. Chemokines are known coordinators of leukocyte migration and our aim was to understand how these molecules influence Treg recruitment at the feto-maternal interface and interfere with pregnancy success. We found that both CCL21 and CCL25 chemokine ligands are present in the uterus before and during pregnancy and their ligands CCR7 and CCR9 are expressed in Tregs from the uterus and lymph nodes draining the uterine region. CCR7 mediated the homing of Treg to the uterus while CCR9 determined the maturation state of uterine DCs and presence of T effector cells, and both critically interfered with implantation if genetically deleted. Our data provide new insights on the mechanisms of tolerance acquisition during pregnancy.
- Copyright © 2013 by The American Association of Immunologists, Inc.