Uterine natural killer cells: from foe to friend in reproduction.

Autores de IIS La Fe

• Indra Diaz Hernandez

  Autor

• Diana Alecsandru Danceanu

  Autor

• Juan Antonio García Velasco

  Autor

• Francisco Domínguez Hernández

  Autor

Grupos

• Biología Reproductiva y Bioingeniería en Reproducción Humana

  

  Leader

  Nicolás Garrido Puchalt

• Endocrinología Reproductiva e Infertilidad

  Leader

  José Remohí Giménez

Abstract

Recurrent miscarriage and pre-eclampsia are common reproductive disorders, but their causes are often unknown. Recent evidence has provided new insight into immune system influences in reproductive disorders. A subset of lymphocytes of the innate immune system known as uterine natural killer (uNK) cells are now recognized as fundamental to achieving embryo implantation and successful pregnancy, but were initially attributed a bad reputation. Indeed, immune therapies have been developed to treat the 'exaggerated' immune response from uNK cells. These treatments have been based on studies of peripheral blood natural killer (pbNK) cells. However, uNK cells and pbNK cells have different phenotypic and functional characteristics. The functions of uNK cells are closely related to their interactions with the extravillous trophoblast cells (EVTs) and spiral arteries, which underlie an essential role in regulating vascular function, controlling trophoblast invasion and promoting placental development. EVTs express MHC molecules of class I HLA-C/E/G/F, while uNK cells express, among other receptors, killer cell immunoglobulin-like receptors (KIRs) that bind to HLA-C or CD94/NKG2A inhibitory receptors, and then bind HLA-E. Associations of certain KIR/HLA-C combinations with recurrent miscarriage, pre-eclampsia, and foetal growth restriction and the interactions between uNK cells, trophoblasts and vascular cells have led to the hypothesis that uNK cells may play a role in embryo implantation.

Keywords

• HLA-C, human pregnancy, immunotherapies, killer cell immunoglobulin-like receptors, materno–foetal interface, uterine natural killer cells