Article
Multidisciplinary Sciences
Sumit Sen Santara, Angela C. Crespo, Sachin Mulik, Cristian Ovies, Selma Boulenouar, Jack L. Strominger, Judy Lieberman
Summary: Zika virus infection during pregnancy can lead to placental damage and fetal birth defects, with limited understanding of the cellular immune response at the maternal-fetal interface. Research has shown that dNK cells in the first trimester are able to kill Zika virus-infected trophoblasts, indicating that certain immune cells protect the fetus by eliminating infected cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Endocrinology & Metabolism
Liman Li, Ting Feng, Weijie Zhou, Yuan Liu, Hong Li
Summary: dNK cells play a crucial role in key placental development processes at the maternal-fetal interface, influencing pregnancy outcomes significantly through secretion of cytokines, chemokines, and angiogenic mediators as well as interactions with other cells. Dysregulation of miRNA in dNK cells may lead to pathological consequences, such as recurrent pregnancy loss, and miRNA expression patterns differ between dNK cells and pNK cells in different trimesters of gestation.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2021)
Article
Medicine, Research & Experimental
Shweta Mahajan, Aria Alexander, Zachary Koenig, Nicholas Saba, Nina Prasanphanich, David A. Hildeman, Claire A. Chougnet, Emily Defranco, Sandra Andorf, Tamara Tilburgs
Summary: Decidual CD8(+) T cells play a critical role in providing immunity to infection and immune tolerance for fetal and placental antigens. These cells include shared blood T cells and unique decidual T cells, and the specificity of decidual CD8(+) T cells is closely related to their function and tissue residency.
Article
Biochemistry & Molecular Biology
Lingling Jiang, Haiyi Fei, Xiaoying Jin, Xiu Liu, Cuiyu Yang, Chao Li, Jianmin Chen, Anran Yang, Jiajuan Zhu, Huihong Wang, Xiaoyang Fei, Songying Zhang
Summary: Extracellular vesicles derived from trophoblasts (T-EVs) secreted HLA-E, promoting the secretion of IFN-gamma and VEGF alpha by decidual NK (dNK) cells from unexplained recurrent spontaneous abortion (URSA) patients to maintain pregnancy. Glycolysis and oxidative phosphorylation (OxPhos) played crucial roles in this process, with glycolysis of dNK cells facilitated by T-EVs depending on mTORC1 activation. Inhibition of T-EV production in mouse models increased susceptibility to embryo absorption, which could be reversed by transferring exogenous Qa-1(+)T-EVs.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Cell Biology
Eliza Grbac, Teresa So, Swati Varshney, Nicholas Williamson, Evdokia Dimitriadis, Ellen Menkhorst
Summary: Research suggests that prednisolone affects the expression of cytokines and protein production in human endometrial stromal fibroblasts (hESF), altering their regulation of trophoblast cells. Decidualization of hESF in the presence of prednisolone enhances trophoblast cell growth and influences the expression of cell motility genes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Immunology
Xiuhong Zhang, Haiming Wei
Summary: Pregnancy is a unique immunological process, with NK cells playing a key role in embryonic development and placenta formation. dNK cells are critical in both normal and pathological pregnancies (such as preeclampsia, recurrent spontaneous abortion, endometriosis, and recurrent implantation failure).
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tamara Gulic, Gordana Laskarin, Lana Glavan, Tanja Grubic Kezele, Herman Haller, Daniel Rukavina
Summary: The study investigated the binding of gp96 to Toll-like receptor (TLR) 4 and CD91 receptors on decidual CD1a(+) DCs in vitro, as well as the influence on the maturation status of CD1a(+) DCs. It was found that gp96 efficiently bound CD91 and TLR4 receptors, leading to the maturation of CD1a(+) DCs and significantly increasing the expression of INF-gamma and IL-15, which could potentially have detrimental effects on ongoing pregnancy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Colin Sparano, Dario Solis-Sayago, Anjali Vijaykumar, Chiara Rickenbach, Marijne Vermeer, Florian Ingelfinger, Gioana Litscher, Andre Fonseca, Caroline Mussak, Maud Mayoux, Christin Friedrich, Cesar Nombela-Arrieta, Georg Gasteiger, Burkhard Becher, Sonia Tugues
Summary: This study comprehensively investigated the origin and turnover of murine group 1 innate lymphoid cells (ILCs) using fate mapping and single-cell transcriptomics. The results showed that circulating natural killer (cNK) cells are continuously replaced throughout life, while tissue-resident ILC1s have tissue-dependent development and turnover. The study revealed two waves of ILC1 emergence, with embryonically derived ILC1s giving rise to a cytotoxic subset and the neonatal wave establishing the full spectrum of ILC1s.
SCIENCE IMMUNOLOGY
(2022)
Article
Cell Biology
Jin Luo, Yaqin Wang, Hsun-Ming Chang, Hua Zhu, Jing Yang, Peter C. K. Leung
Summary: Recurrent pregnancy loss (RPL) is a problem in obstetrics and gynecology, and about 50% of cases remain unexplained. Unexplained RPL (uRPL) is believed to be linked to abnormal endometrial microenvironment. This study found that uRPL patients have lower levels of BMP2 and higher levels of ICAM1 in their endometrial samples. Further research using human endometrial stromal cells (HESCs) and human decidual stromal cells (HDSCs) revealed that BMP2 decreases ICAM1 expression by upregulating ID3 through the ALK3-SMAD4 signaling pathway. This study sheds light on a potential therapeutic target for uRPL.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Immunology
Kornel F. Lakatos, Kathleen Hasselblatt, Vilmos Fulop, Gyorgy Lajos Vegh, Thomas McElrath, Ross S. Berkowitz, Kevin M. Elias
Summary: dNK cells have unique roles in healthy placental formation and anti-tumor immune response. Investigating the immunological mechanisms of their interaction with target cells can provide insights into immune evasion of tumor cells and immunologic miscarriages. A novel protocol has been developed to isolate and culture dNK cells, which can be sustained in cell culture while preserving their phenotype and functionality.
JOURNAL OF REPRODUCTIVE IMMUNOLOGY
(2022)
Review
Immunology
Tao Zhang, Hui-Hui Shen, Xue-Yun Qin, Ming-Qing Li
Summary: This review discusses the metabolic programs and interplay between immune cells at the maternal-fetal interface during pregnancy, highlighting their importance in maintaining pregnancy and suggesting potential therapeutic strategies for preventing pregnancy loss.
IMMUNOLOGICAL REVIEWS
(2022)
Article
Medicine, General & Internal
Nan Liu, Huihui Shen, Zehua Wang, Xueyun Qin, Mingqing Li, Xinyan Zhang
Summary: This study found a decrease in CXCR4(+) NK cells in the decidua of RSA patients during early pregnancy. Co-culturing with trophoblasts increased CXCR4 expression in dNK cells. Additionally, trophoblast autophagy educates dNK landscape through the IGF2-TP53-CXCR4 axis.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Cell Biology
Leela R. L. Davies, Deniz Cizmeci, Wenyue Guo, Corinne Luedemann, Ronika Alexander-Parrish, Lindsay Grant, Raul Isturiz, Christian Theilacker, Luis Jodar, Bradford D. Gessner, Galit Alter
Summary: Streptococcus pneumoniae is a major cause of pneumonia, bacteremia, and meningitis in older adults. Two vaccines, PPSV23 and PCV13, containing S. pneumoniae capsular polysaccharides are currently in use. While both vaccines elicit similar killing activity, PCV13 induces a broader and more durable antibody response with increased functionality.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Physiology
Daniel Esteban Paparini, Esteban Grasso, Laura del Carmen Fernandez, Fatima Merech, Rodrigo Weingrill-Barbano, Simone Correa-Silva, Gustavo Izbizky, Jose Ignacio Abasolo, Vanesa Hauk, Rosanna Ramhorst, Estela Bevilaqcua, Claudia Perez Leiros
Summary: The study investigates the functional profile of circulating monocytes and decidual macrophages in term human pregnancy and their contribution to tissue repair when stimulated with decidual factors and VIP ex vivo. Results show that conditioning monocytes with decidual factors and VIP can support processes required for tissue repair and homeostasis maintenance in term placenta.
Article
Cell Biology
Sigrid Vondra, Anna-Lena Hobler, Andreas Ian Lackner, Johanna Raffetseder, Zala Nikita Mihalic, Andrea Vogel, Leila Saleh, Victoria Kunihs, Peter Haslinger, Markus Wahrmann, Heinrich Husslein, Raimund Oberle, Julia Kargl, Sandra Haider, Paulina Latos, Gernot Schabbauer, Martin Knofler, Jan Ernerudh, Jurgen Pollheimer
Summary: During pregnancy, different macrophage populations are found in the decidua basalis (decB) and decidua parietalis (decP), with decBAMs being CD11chi and efficient inducers of Tregs, while decPAMs exhibit a dendritic cell-like phenotype, enhanced phagocytosis, and the ability to activate T cells. Strikingly, EVT-conditioned media can convert decPAMs into a decBAM phenotype, highlighting the critical role of extravillous trophoblasts (EVTs) in the induction of decB-associated macrophage polarization.
Article
Multidisciplinary Sciences
Qin Li, Torsten B. Meissner, Fang Wang, Ziming Du, Sai Ma, Sarika Kshirsagar, Tamara Tilburgs, Jason D. Buenrostro, Motonari Uesugi, Jack L. Strominger
Summary: HLA-C emerged during the evolution of pregnancy in great apes such as gorillas around 10 to 15 million years ago, playing a dual role in tolerance and immunity at the maternal-fetal interface. ELF3 is a key regulator of HLA-C, forming an autoregulatory feedback loop to establish their expression in trophoblasts. Wrenchnolol disrupts this positive-feedback loop by blocking the binding of MED23 to ELF3, resulting in down-regulation of HLA-C expression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Nadia M. Ikumi, Komala Pillay, Tamara Tilburgs, Thokozile R. Malaba, Sonwabile Dzanibe, Elizabeth Ann L. Enninga, Rana Chakraborty, Mohammed Lamorde, Landon Myer, Saye Khoo, Heather B. Jaspan, Clive M. Gray
Summary: The study found T-cell imbalances in the placenta of HIV-infected pregnant women who initiated ART late in pregnancy, which were related to the blood circulation status of the mother. This may be a causal link to immune changes in newborn infants.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Multidisciplinary Sciences
Sumit Sen Santara, Angela C. Crespo, Sachin Mulik, Cristian Ovies, Selma Boulenouar, Jack L. Strominger, Judy Lieberman
Summary: Zika virus infection during pregnancy can lead to placental damage and fetal birth defects, with limited understanding of the cellular immune response at the maternal-fetal interface. Research has shown that dNK cells in the first trimester are able to kill Zika virus-infected trophoblasts, indicating that certain immune cells protect the fetus by eliminating infected cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Correction
Multidisciplinary Sciences
Tove Lekva, Marie Cecilie Paasche Roland, Mette E. Estensen, Errol R. Norwitz, Tamara Tilburgs, Tore Henriksen, Jens Bollerslev, Kjersti R. Normann, Per Magnus, Ole Kristoffer Olstad, Pal Aukrust, Thor Ueland
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
T. Lekva, M. C. P. Roland, M. E. Estensen, E. R. Norwitz, T. Tilburgs, T. Henriksen, J. Bollerslev, K. R. Normann, P. Magnus, O. K. Olstad, P. Aukrust, T. Ueland
Summary: This study found that the expression of TERC in PBMC was decreased in pregnant women who subsequently developed preeclampsia, suggesting a potential involvement of dysfunctional telomerase biology in the pathophysiology of preeclampsia. Additionally, senescence markers like CAMP and beta-galactosidase were increased in preeclamptic pregnancies, with CAMP remaining elevated even at 5-year follow-up, indicating a continued dysregulation of cellular senescence in PE.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Caroline Junqueira, Angela Crespo, Shahin Ranjbar, Luna B. de Lacerda, Mercedes Lewandrowski, Jacob Ingber, Blair Parry, Sagi Ravid, Sarah Clark, Marie Rose Schrimpf, Felicia Ho, Caroline Beakes, Justin Margolin, Nicole Russell, Kyle Kays, Julie Boucau, Upasana Das Adhikari, Setu M. Vora, Valerie Leger, Lee Gehrke, Lauren A. Henderson, Erin Janssen, Douglas Kwon, Chris Sander, Jonathan Abraham, Marcia B. Goldberg, Hao Wu, Gautam Mehta, Steven Bell, Anne E. Goldfeld, Michael R. Filbin, Judy Lieberman
Summary: This study suggests that SARS-CoV-2 infection in monocytes and macrophages, mediated by antibody uptake, triggers inflammatory cell death and systemic inflammation, which prevents the production of infectious virus but contributes to COVID-19 pathogenesis.
Article
Multidisciplinary Sciences
Ashley L. Severance, Jeremy M. Kinder, Lijun Xin, Ashley R. Burg, Tzu-Yu Shao, Giang Pham, Tamara Tilburgs, Wendy A. Goodman, Sam Mesiano, Sing Sing Way
Summary: During pregnancy, progesterone stimulates the expansion of regulatory T cells to promote immune tolerance, ensuring fetal growth and preventing rejection from the mother's immune system. This study reveals the role of progesterone in promoting fetal tolerance and establishes a molecular link between immune and other physiological adaptations during pregnancy.
Correction
Multidisciplinary Sciences
Sumit Sen Santara, Dian-Jang Lee, Angela Crespo, Jun Jacob Hu, Caitlin Walker, Xiyu Ma, Ying Zhang, Sourav Chowdhury, Karla F. Meza-Sosa, Mercedes Lewandrowski, Haiwei Zhang, Marjorie Rowe, Arthur McClelland, Hao Wu, Caroline Junqueira, Judy Lieberman
Article
Multidisciplinary Sciences
Sumit Sen Santara, Dian-Jang Lee, Angela Crespo, Jun Jacob Hu, Caitlin Walker, Xiyu Ma, Ying Zhang, Sourav Chowdhury, Karla F. Meza-Sosa, Mercedes Lewandrowski, Haiwei Zhang, Marjorie Rowe, Arthur McClelland, Hao Wu, Caroline Junqueira, Judy Lieberman
Summary: Natural killer (NK) cells can recognize externalized calreticulin (ecto-CRT) as an endogenous ligand for the activating receptor NKp46. Recognition of ecto-CRT by NKp46 triggers NK cell signaling and leads to the elimination of ER-stressed cells. This recognition mechanism plays a crucial role in immune surveillance and cancer prevention.
Article
Biochemical Research Methods
Ira Hamilton, Nadia M. Ikumi, Sarika Kshirsagar, Wendy A. Goodman, Tamara Tilburgs
Summary: This study presents a protocol for purifying and culturing HLA-G+ EVTs, the most invasive cells of the placenta that play a crucial role in modulating maternal immune responses. The protocol includes steps for tissue dissection, digestion, centrifugation, and cell sorting, as well as methods for determining EVT function. It provides a comprehensive approach for investigating maternal immune interactions with HLA-G+ EVTs.
Article
Biochemical Research Methods
Nadia M. Ikumi, Zachary Koenig, Shweta Mahajan, Clive M. Gray, Tamara Tilburgs
Summary: This article presents detailed methods for purifying, culturing, and functionally analyzing human placental decidual leukocytes, including dNK, dTreg, dTem, and dM ɸ, from different parts of the placenta. These methods have high clinical relevance in understanding the development of diseases such as villitis and chorioamnionitis.
Article
Medicine, Research & Experimental
Shweta Mahajan, Aria Alexander, Zachary Koenig, Nicholas Saba, Nina Prasanphanich, David A. Hildeman, Claire A. Chougnet, Emily Defranco, Sandra Andorf, Tamara Tilburgs
Summary: Decidual CD8(+) T cells play a critical role in providing immunity to infection and immune tolerance for fetal and placental antigens. These cells include shared blood T cells and unique decidual T cells, and the specificity of decidual CD8(+) T cells is closely related to their function and tissue residency.
Meeting Abstract
Developmental Biology
Tamara Tilburgs
Meeting Abstract
Obstetrics & Gynecology
Sarika Kshirsagar, Tamara Hagen, Tamara Tilburgs
REPRODUCTIVE SCIENCES
(2021)