The role of uterine innate lymphoid cells in early pregnancy

• Applicant: Damián Muzzio, Ph.D.
• Subject Area: Gynaecology and Obstetrics ; Immunology ; Reproductive Medicine, Urology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 457290353

Pregnancy success greatly depends on an adequate implantation, placental development and function. 2800When the underlying mechanisms fail, different pregnancy complications might arise, including early pregnancy loss, preterm labor and preeclampsia. Immune cells play an important role in both physiologic as well as pathologic events during pregnancy. During early pregnancy and labor, a pro-inflammatory immune status prevails, while the rest of the gestation is characterized by a pronounced anti-inflammatory environment. Recently, a new innate cell group has been described to be expressed in fetomaternal interface: the innate lymphoid cells (ILCs). These cells play central roles in different mucosal barriers, influencing the immune response by interacting with other cell types or by producing inflammatory mediators. We hypothesize that at the beginning of pregnancy, (a) ILCs influence trophoblast invasiveness and uterine angiogenesis. In this context, ILCs adapt their antigen presentation strategies (b) to further support fetal tolerance. We propose that physiologic uterine conditions, including pregnancy specific hormonal adaptation and the low oxygen availability to be major determinants of ILC3 function (c). These hypotheses will be tested in both, human as well as mouse models. Employing experimental and descriptive approaches, molecular and functional aspects of in vitro generated ILCs will be elucidated. Our proposed work delivers new information on the role of ILCs at the fetomaternal interface.

• DFG Programme: Research Grants