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decidual nk cells

Ruxandra I Sava, Keith L March, Carl J Pepine
Pregnancy-related hypertension (PHTN) syndromes are a frequent and potentially deadly complication of pregnancy, while also negatively impacting the lifelong health of the mother and child. PHTN appears in women likely to develop hypertension later in life, with the stress of pregnancy unmasking a subclinical hypertensive phenotype. However, distinguishing between PHTN and chronic hypertension is essential for optimal management. Preeclampsia (PE) is linked to potentially severe outcomes and lacks effective treatments due to poorly understood mechanisms...
February 27, 2018: Clinical Cardiology
D Feyaerts, T Kuret, B van Cranenbroek, S van der Zeeuw-Hingrez, O W H van der Heijden, A van der Meer, I Joosten, R G van der Molen
STUDY QUESTION: Is the natural killer (NK) cell receptor repertoire of endometrial NK (eNK) cells tissue-specific? SUMMARY ANSWER: The NK cell receptor (NKR) expression profile in pre-pregnancy endometrium appears to have a unique tissue-specific phenotype, different from that found in NK cells in peripheral blood, suggesting that these cells are finely tuned towards the reception of an allogeneic fetus. WHAT IS KNOWN ALREADY: NK cells are important for successful pregnancy...
February 13, 2018: Human Reproduction
Yuan Zhang, Ying Wang, Ming-Qing Li, Jie Duan, Deng-Xuan Fan, Li-Ping Jin
Decidual immune cells (DICs), consisting of both innate and adaptive immune cells, have a pivotal role in maintaining immune tolerance for normal pregnancy. Our previous study demonstrated that interleukin (IL)-25 stimulates the proliferation of decidual stromal cells (DSCs) in an autocrine manner. However, the role of IL-25 in functional regulation of DICs is largely unknown. Flow cytometry was used to analyze the expression of IL-25 and its receptor (IL-17RB) in DICs, and the effect of IL-25 on the expression of Ki-67, IL-4, IL-10, interferon (IFN)-γ and transforming growth factor (TGF)-β in decidual γδT cells...
February 2018: Experimental and Therapeutic Medicine
Shao-Liang Yang, Tian-Tian Niu, Xue-Lian Li, Da-Jin Li, Ming-Qing Li, Hai-Yan Wang
Recurrent spontaneous abortion (RSA) is a common health problem that affects about 5% of fertile women, when it occurs for unknown reasons, it is called unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine, such as Bu-Shen-Yi-Qi formula which consists of Dangshen, Tusizi, Baizhu, Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable role in the treatment of RSA since ancient times. However, the mechanism of how it takes effect is still not clear. To identify Bu-Shen-Yi-Qi formula could modulate immune condition at maternal-fetal interface via its effect on trophoblasts, HTR-8 of different treatment were co-cultured with peripheral or decidual natural killer (NK) cells, and the receptors such as NKP30 and NKP46 expression on NK cells were measured by flow cytometry (FCM)...
January 15, 2018: Gynecological Endocrinology
Binqing Fu, Yonggang Zhou, Xiang Ni, Xianhong Tong, Xiuxiu Xu, Zhongjun Dong, Rui Sun, Zhigang Tian, Haiming Wei
Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy. However, the role of NK cells in fetal growth is unclear. Here, we have identified a CD49a+Eomes+ subset of NK cells that secreted growth-promoting factors (GPFs), including pleiotrophin and osteoglycin, in both humans and mice. The crosstalk between HLA-G and ILT2 served as a stimulus for GPF-secreting function of this NK cell subset. Decreases in this GPF-secreting NK cell subset impaired fetal development, resulting in fetal growth restriction...
December 19, 2017: Immunity
Paul J Brighton, Yojiro Maruyama, Katherine Fishwick, Pavle Vrljicak, Shreeya Tewary, Risa Fujihara, Joanne Muter, Emma S Lucas, Taihei Yamada, Laura Woods, Raffaella Lucciola, Yie Hou Lee, Satoru Takeda, Sascha Ott, Myriam Hemberger, Siobhan Quenby, Jan Joris Brosens
In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells that control embryo implantation. Here we show that FOXO1 also causes acute senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner. Selective depletion or enrichment of this subpopulation revealed that decidual senescence drives the transient inflammatory response associated with endometrial receptivity...
December 11, 2017: ELife
Rui-Qi Chang, Da-Jin Li, Ming-Qing Li
The survival of allogeneic fetus during pregnancy contradicts the laws of immune responses. Behind this paradoxical phenomenon, the mechanism is quite complex. Indoleamine-2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism. Emerging evidence shows that IDO is expressed at the maternal-fetal interface, including trophoblast cells, decidual stroma cells, decidual immune cells (eg, natural killer cells, T cells, and macrophages), and vascular endothelial cells of decidua and chorion...
November 20, 2017: American Journal of Reproductive Immunology: AJRI
Majid Ahmadi, Samaneh Abdolmohammadi-Vahid, Mahnaz Ghaebi, Leili Aghebati-Maleki, Sanam Dolati, Laya Farzadi, Aliyeh Ghasemzadeh, Kobra Hamdi, Vahid Younesi, Mohammad Nouri, Mehdi Yousefi
RIF (repeated implantation failure) women with immunologic basis and cellular abnormalities may benefit from intravenous immunoglobulins (IVIG) as an immunomodulator based on different studies. In this study, we evaluated the effect of IVIG on the frequency and function of Th17 and Treg cells, as two important subgroups of CD4 + T cells in implantation and pregnancy rates. Seventy-two RIF patients with preconception Th1⁄Th2 ratio and natural killer (NK) cells frequency and activity elevation were selected and divided into two groups; 40 out of 72 received IVIG, aspirin, and heparin (anoxaparin) and constituted the treatment group and 32 patients received aspirin and heparin (anoxaparin) and no IVIG and were the control group...
December 2017: Systems Biology in Reproductive Medicine
D Lissauer, M D Kilby, P Moss
In human pregnancy the maternal immune system plays a critical role in the regulation of many aspects of human reproduction including implantation, placentation and defence against infection. Interest has been focussed on the role of uterine natural killer cells (uNK) in the maternal decidua whereas effector CD4+ and CD8+ T cells have received much less attention despite the observation that they represent a major proportion of decidual leucocytes in the latter phase of pregnancy. A range of recent studies have demonstrated that human decidual T cells are highly differentiated, express a range of cytokines and cytotoxic markers, and demonstrate a unique transcriptional profile characterized by high level expression of genes involved in interferon-signalling...
December 2017: Placenta
Su Liu, Lianghui Diao, Chunyu Huang, Yuye Li, Yong Zeng, Joanne Y H Kwak-Kim
The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus, despite being recognized by the maternal immune cells. Within the innate immune system, decidual natural killer cells and antigen presenting cells (including macrophages and dendritic cells) that comprise a large proportion of the decidual leukocyte populations play an important role in modulating trophoblast invasion, angiogenesis and vascular remodeling. On the other hand, within the adaptive immune system, CD8(+) T cells, effector CD4(+) T cells, Foxp3(+) regulatory T cells and CD4(+)HLA-G(+) suppressor T cells are identified as potential players in maintaining immune tolerance toward the semi-allogeneic fetus...
October 18, 2017: Journal of Reproductive Immunology
Richard M Powell, David Lissauer, Jennifer Tamblyn, Andrew Beggs, Philip Cox, Paul Moss, Mark D Kilby
Immune tolerance during human pregnancy is maintained by a range of modifications to the local and systemic maternal immune system. Lymphoid infiltration is seen at the implantation site of the fetal-maternal interface, and decidual NK cells have been demonstrated to facilitate extravillous trophoblast invasion into maternal decidua during the first trimester, optimizing hemochorial placentation. However, although there is considerable T cell infiltration of the maternal decidua, the functional properties of this T cell response remain poorly defined...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Qiang Fu, Yufei Sun, Yu Tao, Hailan Piao, Xiaoqiu Wang, Xiying Luan, Meirong Du, Dajin Li
PROBLEM: The mechanisms underlying the regulation of decidual natural killer cells (dNKs) at the maternal-fetal interface are unclear. METHOD OF STUDY: Primary trophoblasts (TROs), decidual stromal cells (DSCs), and dNKs were cocultured, and responses to LAIR-2 (LAIR-1 inhibitor) and P4H shRNA (collagen inhibitor) were studied. RESULTS: Coculture of dNKs with primary TROs/DSCs resulted in downregulation of Th1 cytokine production by dNKs. These effects were abrogated by LAIR-2 and P4H shRNA...
October 4, 2017: American Journal of Reproductive Immunology: AJRI
S F Rinaldi, S Makieva, P T Saunders, A G Rossi, J E Norman
STUDY QUESTION: Is labour, both at term and preterm, associated with alterations in decidual lymphocyte densities and widespread changes to the decidual transcriptome? SUMMARY ANSWER: The onset of parturition, both at term and preterm, is associated with widespread gene expression changes in the decidua, many of which are related to inflammatory signalling, but is not associated with changes in the number of any of the decidual lymphocyte populations examined. WHAT IS KNOWN ALREADY: Given its location, directly at the maternal-foetal interface, the decidua is likely to play a pivotal role in the onset of parturition, however, the molecular events occurring in the decidua in association with the onset of labour, both at term and preterm, remain relatively poorly defined...
October 1, 2017: Molecular Human Reproduction
Issaka Yougbaré, Wei-She Tai, Darko Zdravic, Brigitta Elaine Oswald, Sean Lang, Guangheng Zhu, Howard Leong-Poi, Dawei Qu, Lisa Yu, Caroline Dunk, Jianhong Zhang, John G Sled, Stephen J Lye, Jelena Brkić, Chun Peng, Petter Höglund, B Anne Croy, S Lee Adamson, Xiao-Yan Wen, Duncan J Stewart, John Freedman, Heyu Ni
Miscarriage and intrauterine growth restriction (IUGR) are devastating complications in fetal/neonatal alloimmune thrombocytopenia (FNAIT). We previously reported the mechanisms for bleeding diatheses, but it is unknown whether placental, decidual immune cells or other abnormalities at the maternal-fetal interface contribute to FNAIT. Here we show that maternal immune responses to fetal platelet antigens cause miscarriage and IUGR that are associated with vascular and immune pathologies in murine FNAIT models...
August 9, 2017: Nature Communications
Philippe Le Bouteiller, Armand Bensussan
One part of the human placenta in early pregnancy is particularly important for local immunity: the decidua basalis, which is transformed endometrium located at the site of embryo implantation . This placental bed tissue contains both maternal uterine immune cells, including decidual natural killer (NK) cells, the dominant leukocyte population exhibiting a unique phenotype, and fetal extravillous trophoblast which comes into direct contact with maternal decidual cells . To establish a successful placental development and healthy pregnancy outcome, the maternal immune system must tolerate paternal antigens expressed by trophoblast cells yet remain efficient for clearing any local pathogen infection...
2017: F1000Research
Wenwei Guo, Liang Fang, Bo Li, Xifeng Xiao, Shuqiang Chen, Jun Wang, Fang Yang, Lihua Chen, Xiaohong Wang
Human leukocyte antigen (HLA)-G plays a crucial role in conferring fetal-maternal tolerance and ensuring a successful pregnancy. CD56(bright) natural killer (NK) cells accumulate at the maternal decidua in large numbers during pregnancy and are found in direct contact with fetal trophoblasts. There are increasing evidences that decidual NK (dNK) cells are crucial for pregnancy. However, the regulation of dNK cells is mostly unknown. Here, we provide evidences that the secretion function of dNK cells in recurrent spontaneous abortion was impaired, which led to the impairment of the proinvasion and proangiogenesis functions of dNK cells...
2017: Frontiers in Immunology
Kirk P Conrad, Maria Belen Rabaglino, Emiel D Post Uiterweer
In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal decidual, myometrial, immune and vascular cells in the uterine wall. Therefore, aberrant function of anyone or several of these cell-types could theoretically impair placentation leading to the development of preeclampsia. Because trophoblast invasion and spiral artery remodeling occur during the first half of pregnancy, the molecular pathology of fetal placental and maternal decidual tissues following delivery may not be informative about the genesis of impaired placentation, which transpired months earlier...
December 2017: Placenta
Qiang Fu, Xuejing Man, Min Yu, Yongli Chu, Xiying Luan, Hailan Piao, Jiangnan Xue, Changzhu Jin
The development of maternal tolerance to the fetal allograft in critical for the maintenance of the pregnancy, and it is accompanied by the development of a special decidual natural killer (dNK) cell tolerance phenotype. To understand the factors that influence dNK cells during early pregnancy, the present study aimed to identify mesenchymal stem cells (MSCs) from human first‑trimester deciduas, termed decidual MSCs (DMSCs), and to investigate the effect of DMSCs on the regulation of dNK cells via collagen...
September 2017: Molecular Medicine Reports
Liyang Ma, Guanlin Li, Guangming Cao, Yuchun Zhu, Mei-Rong Du, Yangyu Zhao, Hao Wang, Yanlei Liu, Yanyan Yang, Yu-Xia Li, Da-Jin Li, Huixia Yang, Yan-Ling Wang
Decidual NK (dNK) cells, identified as CD56(bright)CD16(-)CD3(-), account for ~70% of lymphocytes within the uterine wall during early pregnancy. Accumulating evidence suggests that tight interactions between placental trophoblasts and dNK cells are critical for trophoblast cell differentiation. However, the underlying mechanism remains to be explored in detail. In the present study, conditioned medium (CM) was collected from cultured primary human dNK cells. Primary cytotrophoblasts (CTBs) or the human trophoblast cell line HTR8/SVneo was treated with dNK-CM and co-cultured with human umbilical vein endothelial cells (HUVECs) in a three-dimensional Matrigel scaffold, and the formation of tube structures was dynamically monitored with live cell imaging...
September 2017: Immunology and Cell Biology
Dorien Feyaerts, Marilen Benner, Bram van Cranenbroek, Olivier W H van der Heijden, Irma Joosten, Renate G van der Molen
Pregnancy requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Despite increasing knowledge, data is lacking on the transition of pre-pregnancy endometrial lymphocytes to a pregnancy state. Here, we immunophenotyped lymphocytes from endometrium (MMC), term decidua parietalis (DPMC), and PBMC for direct comparison. We found that the immune cell composition of MMC and DPMC clearly differ from each other, with less NK-cells, and more NKT-cells and T-cells in DPMC...
June 6, 2017: Scientific Reports
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