scholarly journals A balancing act: mechanisms by which the fetus avoids rejection by the maternal immune system

Reproduction ◽  
2011 ◽  
Vol 141 (6) ◽  
pp. 715-724 ◽  
Author(s):  
J C Warning ◽  
S A McCracken ◽  
J M Morris
Keyword(s):  
Immune Cells ◽  
Vascular Remodeling ◽  
Pregnancy Loss ◽  
Extravillous Trophoblast ◽  
Successful Pregnancy ◽  
Temporal Regulation ◽  
Maternal Immune System ◽  
Inflammatory Processes ◽  
Maternal Immune Response ◽  
Placental Invasion

Successful pregnancy requires strict temporal regulation of maternal immune function to accommodate the growing fetus. Early implantation is facilitated by inflammatory processes that ensure adequate vascular remodeling and placental invasion. To prevent rejection of the fetus, this inflammation must be curtailed; reproductive immunologists are discovering that this process is orchestrated by the fetal unit and, in particular, the extravillous trophoblast. Soluble and particulate factors produced by the trophoblast regulate maternal immune cells within the decidua, as well as in the periphery. The aim of this review is to discuss the action of recently discovered immunomodulatory factors and mechanisms, and the potential effects of dysregulation of such mechanisms on the maternal immune response that may result in pregnancy loss or preeclampsia.

scholarly journals KIR-HLAC genotyping in married couples with early reproductive losses of unknown genesis

2021 ◽  
Vol 29 ◽  
pp. 157-162
Author(s):  
K. O. Sosnina ◽  
D.V. Zastavna ◽  
O.I. Terpyliak
Keyword(s):  
Pregnancy Loss ◽  
Genetic Test ◽  
Significant Risk ◽  
Married Couples ◽  
Successful Pregnancy ◽  
Medical Interventions ◽  
Kir Genes ◽  
Maternal Immune System ◽  
Extraction And Purification ◽  
Reproductive Losses

Aim. KIR-HLAC genotyping in married couples with early idiopathic pregnancy loss. Methods. DNA extraction and purification, PCR-SSP, agarose gel electrophoresis. Results. The spectrum of KIR genes was analyzed and the frequency of KIR genotypes in women with early reproductive losses was established. The most common (77.78 %) was the AB genotype, 20.37 % had the AA genotype, and 1.85 % had the BB genotype. HLAC genotyping of couples with regular early reproductive losses showed the C1/C2 genotype of the HLAC gene in 40.74 % of women and 44.44 % of men. The frequency of C1/C1 genotype in women was 27.78% versus 38.89 % in men. The C2/C2 genotype of the HLAC gene was detected in 31.48 % of women and 12.96 % of men. According to the results of KIR-HLAC analysis of genotyping of married couples with early reproductive losses, a high/significant risk of reproductive losses of immunological genesis was found in 55.56 % of cases. Conclusions. KIR-HLAC genotyping is a genetic test that allows to assess the risks of the embryo being rejected by the maternal immune system, and thus to direct medical interventions in order to achieve a successful pregnancy. Keywords: early reproductive losses, KIR, HLAC.

Regulation of Pregnancy: Evidence for Major Roles by the Uterine and Placental Kisspeptin/KISS1R Signaling Systems

2019 ◽  
Vol 37 (04) ◽  
pp. 182-190 ◽  
Author(s):  
Sally Radovick ◽  
Andy V. Babwah
Keyword(s):  
Stromal Cells ◽  
Pregnancy Loss ◽  
Therapeutic Agent ◽  
Recurrent Pregnancy Loss ◽  
Embryo Implantation ◽  
Extravillous Trophoblast ◽  
Migration And Invasion ◽  
Decidual Cell ◽  
Signaling Systems ◽  
Placental Invasion

AbstractSeveral studies provide strong evidence suggesting that in addition to central kisspeptin/KISS1R signaling, the peripheral uterine- and placental-based kisspeptin/KISS1R signaling systems are major regulators of pregnancy. Specifically, the evidence suggests that the uterine-based system regulates embryo implantation and decidualization, while both the uterine- and placental-based systems regulate placentation. Uterine kisspeptin and KISS1R regulate embryo implantation by controlling the availability of endometrial glandular secretions, like leukemia inhibitory factor, which are essential for embryo adhesion to the uterine epithelium. As for decidualization, the data suggest that decidualized stromal cells express KISS1R and secrete kisspeptin-inhibiting decidual cell motility and thereby indirectly regulate embryo and placental invasion of the uterus. Similarly, for placentation, placental kisspeptin and KISS1R negatively regulate extravillous trophoblast migration and invasion and thereby directly control placental invasion of the uterus. Having recognized a significant role for the uterine- and placental-based kisspeptin/KISS1R signaling systems regulating pregnancy, the future looks promising for the development of kisspeptin and KISS1R as prognostic and diagnostic markers of pregnancy disorders and the use of kisspeptin as a therapeutic agent in the prevention and treatment of conditions such as recurring implantation failure, recurrent pregnancy loss, and preeclampsia.

scholarly journals Single-cell profiling of the human decidual immune microenvironment in patients with recurrent pregnancy loss

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chuang Guo ◽  
Pengfei Cai ◽  
Liying Jin ◽  
Qing Sha ◽  
Qiaoni Yu ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Immune Cell ◽  
Recurrent Miscarriage ◽  
Extravillous Trophoblast ◽  
Cellular Interactions ◽  
Immune Microenvironment ◽  
Immune Cell Subsets

AbstractMaintaining homeostasis of the decidual immune microenvironment at the maternal–fetal interface is essential for placentation and reproductive success. Although distinct decidual immune cell subpopulations have been identified under normal conditions, systematic understanding of the spectrum and heterogeneity of leukocytes under recurrent miscarriage in human deciduas remains unclear. To address this, we profiled the respective transcriptomes of 18,646 primary human decidual immune cells isolated from patients with recurrent pregnancy loss (RPL) and healthy controls at single-cell resolution. We discovered dramatic differential distributions of immune cell subsets in RPL patients compared with the normal decidual immune microenvironment. Furthermore, we found a subset of decidual natural killer (NK) cells that support embryo growth were diminished in proportion due to abnormal NK cell development in RPL patients. We also elucidated the altered cellular interactions between the decidual immune cell subsets in the microenvironment and those of the immune cells with stromal cells and extravillous trophoblast under disease state. These results provided deeper insights into the RPL decidual immune microenvironment disorder that are potentially applicable to improve the diagnosis and therapeutics of this disease.

Platelets: Angels and demons dancing on the immune stage. Nutrition conducts the orchestra

2020 ◽  
Vol 20 ◽  
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Matteo Antonio Russo ◽  
Emilio Jirillo
Keyword(s):  
Platelet Function ◽  
Immune Cells ◽  
Dual Role ◽  
Immune Functions ◽  
Omega 3 ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Adaptive Immune Cells ◽  
Immune Mediated ◽  
Inflammatory Processes

Background: Platelets are cellular fragments derived from bone-marrow megacaryocytes and they are mostly involved in haemostasis and coagulation. However, according to recent data, platelets are able to perform novel immune functions. In fact, they possess a receptorial armamentarium on their membrane for interacting with innate and adaptive immune cells. In addition, platelets also secrete granules which contain cytokines and chemokines for activating and recruiting even distant immune cells. Objectives: The participation of platelets in inflammatory processes will be discussed also in view of their dual role in terms of triggering or resolving inflammation. Involvement of platelets in disease will be illustrated, pointing to their versatile function to either up- or down-regulate pathological mechanisms. Finally, despite the availability of some anti-platelet agents, such as aspirin, dietary manipulation of platelet function is currently investigated. In this regard, special emphasis will be placed on dietary omega-3 polyunsaturated fatty acids (PUFAs) and polyphenol effects on platelets. Conclusion: Platelets play a dual role in inflammatory-immune-mediated diseases either activating or deactivating immune cells. Diet based on substances, such as omega-3 PUFAs and polyphenols, may act as a modulator of platelet function, even if more clinical trials are needed to corroborate such a contention.

scholarly journals HMGA1 Is a Potential Driver of Preeclampsia Pathogenesis by Interference with Extravillous Trophoblasts Invasion

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 822
Author(s):  
Keiichi Matsubara ◽  
Yuko Matsubara ◽  
Yuka Uchikura ◽  
Katsuko Takagi ◽  
Akiko Yano ◽  
...  
Keyword(s):  
Protein A ◽  
High Mobility ◽  
Extravillous Trophoblast ◽  
High Mobility Group Protein ◽  
Successful Pregnancy ◽  
Group Protein ◽  
Serious Disease ◽  
Proliferation And Invasion ◽  
Extravillous Trophoblasts ◽  
Fertilized Egg

Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure–derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.

scholarly journals Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 730
Author(s):  
Moritz Peiseler ◽  
Frank Tacke
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Disease Progression ◽  
Immune Cells ◽  
Nonalcoholic Steatohepatitis ◽  
Adaptive Immune System ◽  
Nonalcoholic Fatty Liver ◽  
Inflammatory Processes ◽  
New Treatment ◽  
End Stage

Nonalcoholic fatty liver disease (NAFLD) is a rising chronic liver disease and comprises a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to end-stage cirrhosis and risk of hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is multifactorial, but inflammation is considered the key element of disease progression. The liver harbors an abundance of resident immune cells, that in concert with recruited immune cells, orchestrate steatohepatitis. While inflammatory processes drive fibrosis and disease progression in NASH, fueling the ground for HCC development, immunity also exerts antitumor activities. Furthermore, immunotherapy is a promising new treatment of HCC, warranting a more detailed understanding of inflammatory mechanisms underlying the progression of NASH and transition to HCC. Novel methodologies such as single-cell sequencing, genetic fate mapping, and intravital microscopy have unraveled complex mechanisms behind immune-mediated liver injury. In this review, we highlight some of the emerging paradigms, including macrophage heterogeneity, contributions of nonclassical immune cells, the role of the adaptive immune system, interorgan crosstalk with adipose tissue and gut microbiota. Furthermore, we summarize recent advances in preclinical and clinical studies aimed at modulating the inflammatory cascade and discuss how these novel therapeutic avenues may help in preventing or combating NAFLD-associated HCC.

Inflammatory Mechanisms in Parkinson’s Disease: From Pathogenesis to Targeted Therapies

2021 ◽  
pp. 107385842199226
Author(s):  
Stellina Y. H. Lee ◽  
Nathanael J. Yates ◽  
Susannah J. Tye
Keyword(s):  
Parkinson’S Disease ◽  
Central Nervous System ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Immune Cells ◽  
Critical Factor ◽  
Neurodegenerative Process ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Novel Target

Inflammation is a critical factor contributing to the progressive neurodegenerative process observed in Parkinson’s disease (PD). Microglia, the immune cells of the central nervous system, are activated early in PD pathogenesis and can both trigger and propagate early disease processes via innate and adaptive immune mechanisms such as upregulated immune cells and antibody-mediated inflammation. Downstream cytokines and gene regulators such as microRNA (miRNA) coordinate later disease course and mediate disease progression. Biomarkers signifying the inflammatory and neurodegenerative processes at play within the central nervous system are of increasing interest to clinical teams. To be effective, such biomarkers must achieve the highest sensitivity and specificity for predicting PD risk, confirming diagnosis, or monitoring disease severity. The aim of this review was to summarize the current preclinical and clinical evidence that suggests that inflammatory processes contribute to the initiation and progression of neurodegenerative processes in PD. In this article, we further summarize the data about main inflammatory biomarkers described in PD to date and their potential for regulation as a novel target for disease-modifying pharmacological strategies.

scholarly journals Influence of Estrogens on Uterine Vascular Adaptation in Normal and Preeclamptic Pregnancies

2020 ◽  
Vol 21 (7) ◽  
pp. 2592 ◽  
Author(s):  
Maurizio Mandalà
Keyword(s):  
Heart Rate ◽  
Vascular Remodeling ◽  
Uterine Artery ◽  
Molecular Mechanisms ◽  
Artery Wall ◽  
Successful Pregnancy ◽  
Uteroplacental Blood Flow ◽  
Pathological Pregnancy ◽  
Estrogenic Regulation ◽  
Circulating Levels

During pregnancy, the maternal cardiovascular system undergoes significant changes, including increased heart rate, cardiac output, plasma volume, and uteroplacental blood flow (UPBF) that are required for a successful pregnancy outcome. The increased UPBF is secondary to profound circumferential growth that extends from the downstream small spiral arteries to the upstream conduit main uterine artery. Although some of the mechanisms underlying uterine vascular remodeling are, in part, known, the factors that drive the remodeling are less clear. That higher circulating levels of estrogens are positively correlated with gestational uterine vascular remodeling suggests their involvement in this process. Estrogens binding to the estrogen receptors expressed in cytotrophoblast cells and in the uterine artery wall stimulate an outward hypertrophic remodeling of uterine vasculature. In preeclampsia, generally lower concentrations of estrogens limit the proper uterine remodeling, thereby reducing UPBF increases and restricting the growth of the fetus. This review aims to report estrogenic regulation of the maternal uterine circulatory adaptation in physiological and pathological pregnancy that favors vasodilation, and to consider the underlying molecular mechanisms by which estrogens regulate uteroplacental hemodynamics.

scholarly journals Mast Cells May Regulate The Anti-Inflammatory Activity of IL-37

2019 ◽  
Vol 20 (15) ◽  
pp. 3701 ◽  
Author(s):  
Theoharis C. Theoharides ◽  
Irene Tsilioni ◽  
Pio Conti
Keyword(s):  
Mast Cells ◽  
Immune Cells ◽  
Therapeutic Agents ◽  
Biologically Active ◽  
Inflammatory Activity ◽  
Allergic Reactions ◽  
Regulatory Cytokine ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Novel Therapeutic

Mast cells are unique immune cells involved in allergic reactions, but also in immunity and inflammation. Interleukin 37 (IL-37) has emerged as an important regulatory cytokine with ability to inhibit immune and inflammatory processes. IL-37 is made primarily by macrophages upon activation of toll-like receptors (TLR) leading to generation of mature IL-37 via the action of caspase 1. In this review, we advance the premise that mast cells could regulate the anti-inflammatory activity of the IL-37 via their secretion of heparin and tryptase. Extracellular IL-37 could either dimerize in the presence of heparin and lose biological activity, or be acted upon by proteases that can generate even more biologically active IL-37 forms. Molecules that could selectively inhibit the secretion of mast cell mediators may, therefore, be used together with IL-37 as novel therapeutic agents.

Sign in / Sign up

Export Citation Format

Share Document