Decidual natural killer cells and the immune microenvironment at the maternal-fetal interface

Problem: Decidual natural killer (dNK) cells play key roles in maternal-fetal immune regulation, trophoblast invasion, and vascular remodeling, and most dNK cell populations are CD56 bright CD16 − NK cells. However, the enrichment and redistribution of dNK cells in the local decidua have not been clarified yet. Method of study:A total of 45 women with normal pregnancies and 8 unexplained recurrent spontaneous abortion (RSA) patients were included. We isolated primary human dNK (n = 53) and peripheral blood NK (pNK) cells (n = 5) from specimen and analyzed CD56, CD82, and CD29 by flow cytometry (FCM). We assessed their adhesion ability by cell counts of NK cells adhered to decidual stromal cells (DSCs) in a co-culture system. Results:We found that RSA patients had more CD56 dim dNK cells with lower CD82 and higher CD29 than women with normal pregnancies. There were negative correlations of CD82 to CD29 on CD56 dim and CD56 + dNK cells. In normal pregnancies, dNK cells had lower CD82 and higher CD29 expression with a stronger adhesion ability than pNK cells. Blocking CD82 on dNK cells increased the adhesive ability and CD29 expression, while blocking CD29 decreased the adhesive ability. Co-culturing dNK cells with trophoblast cells decreased CD82 expression and increased the adhesive ability of dNK cells and the percentage of CD56 bright NK cells, while blocking trophoblast-derived CXCL12 increased CD82 expression, decreased CD29 expression, and impaired the adhesive ability of NK cells. Conclusion: Trophoblast cells enhance the adhesive ability of NK cells to DSCs viathe CXCL12/CD82/CD29 signaling pathway and contribute to CD56 bright NK cell enrichment in the uterus. K E Y W O R D S abortion, adhesion, CD29, CD82, CXC12, decidua, NK, trophoblasts How to cite this article: Lu H, Jin L-P, Huang H-L, et al. Trophoblast-derived CXCL12 promotes CD56 bright CD82 − CD29 + NK cell enrichment in the decidua.Am J Reprod Immunol. 2020;83:e13203.

Section: Trophoblast-derived Cxcl12 Increases Cd56 Bright Cd82 − CDmentioning

confidence: 99%

Section: Trophoblast-derived Cxcl12 Increases Cd56 Bright Cd82 − CDmentioning

confidence: 99%

Trophoblast‐derived CXCL12 promotes CD56^brightCD82⁻CD29⁺ NK cell enrichment in the decidua

Han

Jin

Huang

et al. 2019

“…95 Decidual macrophages in early pregnancy can be divided into 2 groups: CD209 + macrophages, which account for 70% of decidual macrophages and are responsive toward infection in the decidua and chorionic inflammation, and CD209 − macrophages, which express higher levels of IL-10 at the basic level or from stimulation with LPS than CD209 + macrophages and whose features tend to be the M2 type. 100 Decidual macrophages are also key immunoregulators at the maternal-fetal interface under local environmental cues from different lymphocyte populations. They not only monitor innate NK cell responses, but are also proficient in regulating adaptive T-cell responses.…”

Section: Mel Atonin and Recurrent S P Ontaneous Abortionmentioning

confidence: 99%

Pleiotropic roles of melatonin in endometriosis, recurrent spontaneous abortion, and polycystic ovary syndrome

Yang

Zhou

et al. 2018

Melatonin is a neurohormone synthesized from the aromatic amino acid tryptophan mainly by the pineal gland of mammals. Melatonin acts as a broad-spectrum antioxidant, powerful free radical scavenger, anti-inflammatory agent, anticarcinogenic factor, sleep inducer and regulator of the circadian rhythm, and potential immunoregulator. Melatonin and reproductive system are interrelated under both physiological and pathological conditions. Oxidative stress, inflammation, and immune dysregulation are associated with the pathogenesis of the female reproductive system which causes endometriosis (EMS), recurrent spontaneous abortion (RSA), and polycystic ovary syndrome (PCOS). Accumulating studies have indicated that melatonin plays pleiotropic and essential roles in these obstetrical and gynecological disorders and would be a candidate therapeutic drug to regulate inflammation and immune function and protect special cells or organs. Here, we systematically review the pleiotropic roles of melatonin in EMS, RSA, and PCOS to explore its pathological implications and treatment potential.

“…Leukocytes account for 30%‐40% of total cells in the decidua of early pregnancy . As summarized in Figure and Table , natural killer (NK) cells are the predominant immune cell population (50%‐70%), and macrophages (Mφ) account for ~20%, whereas T cells account for 2%‐20% of the immune cell population in the decidua of eutopic pregnancy in the first trimester.…”

Section: Introductionmentioning

confidence: 99%

Alteration of the immune cell profiles in the pathophysiology of tubal ectopic pregnancy

Wang

Lee

et al. 2019

Tubal ectopic pregnancy (TEP) refers to implantation of conceptus in the fallopian tube. It makes up over 98% of ectopic pregnancy (EP), which is the leading cause of maternal morbidity and mortality in the first trimester of pregnancy. Immune cells at the maternal-fetal interface play important roles in the process of embryo implantation, stroma decidualization, and early placental development. Alterations in the composition, phenotype, and activity of the immune cells in the fallopian tubes contribute toward the onset of TEP. In this review, we compare the leukocytic proportions in decidua of normal pregnancy, and in decidua and fallopian tubes of TEP. The possible functions of these immune cells in the pathophysiology of TEP are also discussed. K E Y W O R D Sfallopian tube, macrophages, natural killer cell, T cell, tubal ectopic pregnancy