Gormaz López, Andrea

Universitat Autònoma de Barcelona. Facultat de Biociències

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Th2 profile (developed by uNK cells and other cells of the immune system) Immunomodulation during pregnancy Modulates the response of other cell types . IL-10 produced by uNK influences dendritic cells by inhibiting their functions Loss of cytotoxic activity Due to the phenotype + interaction with HLA-G Protection of fetal cells and trophoblast invasion Produce grow factors  VEGF (Vascular endothelial growth factor) + PIGF (placenta grow factor) Involved in decidualization processes + Uterine artery remodeling  + Differentiation, growth and invasion of the decidua Presents chemokines CXCR4 and interacts with CXCL12 (in trophoblasts cells) Allows traffic of these cells Uterine Natural Killer  vs. Peripheral Natural Killer uNK pNK Abundance 70% of human decidua 10-25% of lymphocytes in blood Origin Presence in the decidua: Homing from peripheral blood because of interaction with the endothelial cell adhesion molecules Proliferation and differentiation in situ Bone marrow stem cells Dependent differentiation: SCF, IL-15, IL-7 Receptors CD56Bright            CD16-   CD56Bright CD16dim  (1% ) CD56dim CD16bright  (99%) Functions Invasion of the extravillius trophoblast. It will penetrate into the maternal’s decidua and the miometrium.  Remodeling of the uterine spiral arteries.  Innate response.  Response against intracellular pathogens, the most common viral infections. Regulation of adaptive responses and hematopoiesis Introduction: Uterine Natural Killer cells are a subtype of NK cells with very distinct and important features, these features will give these cells functions that are essential in certain stages of development. The main difference between uterine NK cells and peripheral NK cells rests in their loss of cytotoxic activity and the production of cytokines that produces a favorable environment for pregnancy. These uNK cells are the most numerous leukocytes in early pregnancy. Metodology: Literature search in PubMed and webs of science. Selection of articles and literature reviews of recent years. Andrea Gormaz López    Grau de Biologia   Universitat Autònoma de Barcelona UTERINE NK CELLS AND PREGNANCY References:   1. Chrysoula Dosiu and Linda C. Giudice. 2005. Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives. Endocrine Reviews, 26(1): 44-62. 2. Szekeres-Bartho, J. Symposium: Current Knowledge on natural killer cells, pregnancy and pre-eclampsia. Regulation of NK cell cytotoxicity during pregnancy. 2008. Reproductive BioMedicine Online. Vol 16 No 2. 211-217.   3. Genevieve Eastabrook, BSc, MD, Yuxiang Hu, MSc, Peter von Dadelszen, MB, ChB, DPhil, FRCSC. The role of Decidual Naural Killer Cells in Normal Placentation and in the Pathogenesis of Preeclampsia. 2008. Obstetrics.30(6): 467-476.  4. G.E Lash, S.C Robson, J.N Bulmer. 2010. Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta 31. Vol.24: 87-92 .    Conclusions:   • Clear evidence of a subset of NK cells, NK decidual cells, with specific and different characteristics. One of the most important features is the loss of the cytotoxic capacity and the modulation of the environment with cytokines.  • Important role in the development of pregnancy by promoting trophoblast invasion and spiral artery remodeling. • The HLA-G present in trophoblast causes immunomodulatory action in different cell populations and inhibits usual functions in these cells compared to other tissues and other environments. • The interaction of HLA-G with uNK particularly, contributes to the production of a favorable microenvironment tissue tolerance and inhibition of cytotoxic activity. • The interaction with HLA-G and the microenvironment (profile Th2) generated by uNK cells prevent rejection of pregnancy. They do not express the activator receptor.  Action of HLA-G in trophoblasts cells Action of uNK cells during pregnancy Decreases presentation and inhibits maturation Decreases the ability to present fetal antigens Apoptosis Replacement of pre-existing maternal endothelial cells and contribution to the  remodelation of the spiral artery Inhibits allogeneic reactivity + Inhibits cytotoxic function + Inhibits proliferation  Prevents reactivity against fetal cells Inhibits cytotoxic function + Inhibits proliferation  Prevents attack of fetal cells Inhibits cytotoxic activity + helps produce a favorable microenvironment for the development of tolerance. Inhibits the ability of lysing the fetal cells uNK Interaction of HLA-G present in trophoblast cells with different immune cells present in the pregnancy decidua. Hunt, et al. 2005. HLA-G and immune tolerance in pregnancy (review). The FASEB Journal. Vol.19. 681-693. (modified image). Successful pregnancy 

Uterine nk cells and pregnancy

http://ddd.uab.cat/pub/tfg/2014/123513/TFG_andreagormazlopez.pdf

Uterine nk cells and pregnancy

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