Proliferation of Uterine Natural Killer Cells Is Induced by Human Chorionic Gonadotropin and Mediated via the Mannose Receptor

• Published in: Endocrinology (Philadelphia) 2009-06, Vol.150 (6), p.2882-2888
• Main Authors: Kane, Nicole, Kelly, Rodney, Saunders, Philippa T. K, Critchley, Hilary O. D
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cell Proliferation; Chorionic gonadotropin; Chorionic Gonadotropin - metabolism; Chorionic Gonadotropin - pharmacology; Decidua - cytology; Decidua - drug effects; Decidua - metabolism; Endometrium; Endometrium - cytology; Endometrium - drug effects; Endometrium - metabolism; Female; Fundamental and applied biological sciences. Psychology; Glycoproteins; Gonadotropins; Humans; Immune system; Killer Cells, Natural - cytology; Killer Cells, Natural - drug effects; Killer Cells, Natural - metabolism; Lectins, C-Type - metabolism; Luteinizing hormone; Mannose; Mannose - pharmacology; Mannose Receptor; Mannose-Binding Lectins - metabolism; Natural killer cells; Pituitary (anterior); Pregnancy; Receptors; Receptors, Cell Surface - metabolism; Receptors, LH - metabolism; Uterus; Uterus - cytology; Uterus - drug effects; Uterus - metabolism; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2008-1309

The endometrial lining of the human uterus contains a population of phenotypically distinct (CD56bright, CD16dim), tissue-specific, natural killer [uterine natural killer (uNK)] cells that play a key role in the establishment of a successful pregnancy. An increase in the number of endometrial uNK cells occurs when the conceptus implants, and there is a further increase during the early stages of placentation. Here, we describe studies that have identified human chorionic gonadotrophin (hCG), a glycoprotein synthesized by the preimplantation conceptus, as a novel regulator of uNK cell proliferation. The impact of hCG on uNK cells was mediated via the mannose receptor (CD206) rather than by the classical hCG/LH receptor that was not expressed. The mannose receptor and hCG were colocalized on the surface of uNK cells, and proliferation did not occur if cells were incubated with deglycosylated hCG or intact hCG in the presence of excess d-Mannose. These novel observations provide new insight into the endocrine-immune dialogue that exists between the conceptus and immune cells within the receptive endometrium, and have implications for the role of uNK cell-trophoblast interactions and pregnancy outcome. These studies have identified chorionic gonadotrophin (hCG), a glycoprotein synthesized by the pre-implantation conceptus, as a novel regulator of uNK cell proliferation.