scholarly journals Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance

2021 ◽  
Vol 12 ◽  
Author(s):  
Ling Xu ◽  
Yanhong Li ◽  
Yifei Sang ◽  
Da-Jin Li ◽  
Meirong Du
Keyword(s):  
Immune Tolerance ◽  
Immune Cells ◽  
Direct Interaction ◽  
Basic Research ◽  
Normal Pregnancy ◽  
Therapeutic Strategies ◽  
Maternal Immune System ◽  
Reproductive Immunity ◽  
Clinical Transformation ◽  
Fine Adjustment

The success of pregnancy relies on the fine adjustment of the maternal immune system to tolerate the allogeneic fetus. Trophoblasts carrying paternal antigens are the only fetal-derived cells that come into direct contact with the maternal immune cells at the maternal–fetal interface. The crosstalk between trophoblasts and decidual immune cells (DICs) via cell–cell direct interaction and soluble factors such as chemokines and cytokines is a core event contributing to the unique immunotolerant microenvironment. Abnormal trophoblasts–DICs crosstalk can lead to dysregulated immune situations, which is well known to be a potential cause of a series of pregnancy complications including recurrent spontaneous abortion (RSA), which is the most common one. Immunotherapy has been applied to RSA. However, its development has been far less rapid or mature than that of cancer immunotherapy. Elucidating the mechanism of maternal–fetal immune tolerance, the theoretical basis for RSA immunotherapy, not only helps to understand the establishment and maintenance of normal pregnancy but also provides new therapeutic strategies and promotes the progress of immunotherapy against pregnancy-related diseases caused by disrupted immunotolerance. In this review, we focus on recent progress in the maternal–fetal immune tolerance mediated by trophoblasts–DICs crosstalk and clinical application of immunotherapy in RSA. Advancement in this area will further accelerate the basic research and clinical transformation of reproductive immunity and tumor immunity.

scholarly journals Role of Transforming Growth Factor-β1 in Regulating Fetal-Maternal Immune Tolerance in Normal and Pathological Pregnancy

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongyong Yang ◽  
Fangfang Dai ◽  
Mengqin Yuan ◽  
Yajing Zheng ◽  
Shiyi Liu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Transforming Growth Factor Β ◽  
Normal Pregnancy ◽  
Cell Functions ◽  
Tgf Β1

Transforming growth factor-β (TGF-β) is composed of three isoforms, TGF-β1, TGF-β2, and TGF-β3. TGF-β1 is a cytokine with multiple biological functions that has been studied extensively. It plays an important role in regulating the differentiation of immune cells and maintaining immune cell functions and immune homeostasis. Pregnancy is a carefully regulated process. Controlled invasion of trophoblasts, precise coordination of immune cells and cytokines, and crosstalk between trophoblasts and immune cells play vital roles in the establishment and maintenance of normal pregnancy. In this systematic review, we summarize the role of TGF-β1 in regulating fetal-maternal immune tolerance in healthy and pathological pregnancies. During healthy pregnancy, TGF-β1 induces the production of regulatory T cells (Tregs), maintains the immunosuppressive function of Tregs, mediates the balance of M1/M2 macrophages, and regulates the function of NK cells, thus participating in maintaining fetal-maternal immune tolerance. In addition, some studies have shown that TGF-β1 is dysregulated in patients with recurrent spontaneous abortion or preeclampsia. TGF-β1 may play a role in the occurrence and development of these diseases and may be a potential target for the treatment of these diseases.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Low Dose ◽  
Innate Immune ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Atp Production ◽  
Dose Dependent

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.

scholarly journals Sphingolipid lysosomal storage diseases: from bench to bedside

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Muna Abed Rabbo ◽  
Yara Khodour ◽  
Laurie S. Kaguni ◽  
Johnny Stiban
Keyword(s):  
Basic Research ◽  
Lysosomal Storage Diseases ◽  
Therapeutic Strategies ◽  
Clinical Applications ◽  
Late Nineteenth Century ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
The Past ◽  
Health And Disease ◽  
General Aspects

AbstractJohann Ludwig Wilhelm Thudicum described sphingolipids (SLs) in the late nineteenth century, but it was only in the past fifty years that SL research surged in importance and applicability. Currently, sphingolipids and their metabolism are hotly debated topics in various biochemical fields. Similar to other macromolecular reactions, SL metabolism has important implications in health and disease in most cells. A plethora of SL-related genetic ailments has been described. Defects in SL catabolism can cause the accumulation of SLs, leading to many types of lysosomal storage diseases (LSDs) collectively called sphingolipidoses. These diseases mainly impact the neuronal and immune systems, but other systems can be affected as well. This review aims to present a comprehensive, up-to-date picture of the rapidly growing field of sphingolipid LSDs, their etiology, pathology, and potential therapeutic strategies. We first describe LSDs biochemically and briefly discuss their catabolism, followed by general aspects of the major diseases such as Gaucher, Krabbe, Fabry, and Farber among others. We conclude with an overview of the available and potential future therapies for many of the diseases. We strive to present the most important and recent findings from basic research and clinical applications, and to provide a valuable source for understanding these disorders.

scholarly journals Cell Death in Coronavirus Infections: Uncovering Its Role during COVID-19

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1585
Author(s):  
Annamaria Paolini ◽  
Rebecca Borella ◽  
Sara De Biasi ◽  
Anita Neroni ◽  
Marco Mattioli ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Cells ◽  
Viral Infections ◽  
Virus Entry ◽  
Therapeutic Strategies ◽  
The Other ◽  
Cytokine Storm ◽  
Cytokines And Chemokines ◽  
Cell Death Mechanisms ◽  
The One

Cell death mechanisms are crucial to maintain an appropriate environment for the functionality of healthy cells. However, during viral infections, dysregulation of these processes can be present and can participate in the pathogenetic mechanisms of the disease. In this review, we describe some features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some immunopathogenic mechanisms characterizing the present coronavirus disease (COVID-19). Lymphopenia and monocytopenia are important contributors to COVID-19 immunopathogenesis. The fine mechanisms underlying these phenomena are still unknown, and several hypotheses have been raised, some of which assign a role to cell death as far as the reduction of specific types of immune cells is concerned. Thus, we discuss three major pathways such as apoptosis, necroptosis, and pyroptosis, and suggest that all of them likely occur simultaneously in COVID-19 patients. We describe that SARS-CoV-2 can have both a direct and an indirect role in inducing cell death. Indeed, on the one hand, cell death can be caused by the virus entry into cells, on the other, the excessive concentration of cytokines and chemokines, a process that is known as a COVID-19-related cytokine storm, exerts deleterious effects on circulating immune cells. However, the overall knowledge of these mechanisms is still scarce and further studies are needed to delineate new therapeutic strategies.

Exploration of beneficial and deleterious effects of inflammation in stroke: dynamics of inflammation cells

2009 ◽  
Vol 367 (1908) ◽  
pp. 4699-4716 ◽  
Author(s):  
Taïssia Lelekov-Boissard ◽  
Guillemette Chapuisat ◽  
Jean-Pierre Boissel ◽  
Emmanuel Grenier ◽  
Marie-Aimée Dronne
Keyword(s):  
Immune Cells ◽  
Blood Cells ◽  
Inflammatory Process ◽  
Living Cells ◽  
Therapeutic Strategies ◽  
Brain Parenchyma ◽  
Brain Cell ◽  
Cytokines And Chemokines ◽  
The Brain

The inflammatory process during stroke consists of activation of resident brain microglia and recruitment of leucocytes, namely neutrophils and monocytes/macrophages. During inflammation, microglial cells, neutrophils and macrophages secrete inflammatory cytokines and chemokines, and phagocytize dead cells. The recruitment of blood cells (neutrophils and macrophages) is mediated by the leucocyte–endothelium interactions and more specifically by cell adhesion molecules. A mathematical model is proposed to represent the dynamics of various brain cells and of immune cells (neutrophils and macrophages). This model is based on a set of six ordinary differential equations and explores the beneficial and deleterious effects of inflammation, respectively phagocytosis by immune cells and the release of pro-inflammatory mediators and nitric oxide (NO). The results of our simulations are qualitatively consistent with those observed in experiments in vivo and would suggest that the increase of phagocytosis could contribute to the increase of the percentage of living cells. The inhibition of the production of cytokines and NO and the blocking of neutrophil and macrophage infiltration into the brain parenchyma led also to the improvement of brain cell survival. This approach may help to explore the respective contributions of the beneficial and deleterious roles of the inflammatory process in stroke, and to study various therapeutic strategies in order to reduce stroke damage.

Interactions of lactoferrin with cells involved in immune functionThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

2006 ◽  
Vol 84 (3) ◽  
pp. 282-290 ◽  
Author(s):  
Dominique Legrand ◽  
Elisabeth Elass ◽  
Mathieu Carpentier ◽  
Joël Mazurier
Keyword(s):  
Immune Cells ◽  
Host Response ◽  
Review Process ◽  
Peer Review Process ◽  
Direct Interaction ◽  
Antimicrobial Activities ◽  
Nuclear Targeting ◽  
Cellular Targets ◽  
Anti Inflammatory ◽  
Selection Of

The antimicrobial activities of lactoferrin (Lf) depend on its capacity to bind iron and on its direct interaction with the surface of microorganisms. Its protective effect also extends to the regulation of the host response to infections. Depending on the immune status of an individual, Lf can have anti-inflammatory properties that downregulate the immune response and prevent septic shock and damage to tissues. It also acts as a promoter of the activation, differentiation, and (or) proliferation of immune cells. Although most of the anti-inflammatory activities are correlated with the neutralization of proinflammatory molecules by Lf, the promoting activity seems to be related to a direct effect of Lf on immune cells. Although the mechanisms that govern these activities are not clearly defined, and probably differ from cell to cell, several cellular targets and possible mechanisms of action are highlighted. The majority of the molecular targets at the surface of cells are multiligand receptors but, interestingly, most of them have been reported as signaling, endocytosis, and nuclear-targeting molecules. This review focuses on the known and putative mechanisms that allow the immunoregulating effect of Lf in its interactions with immune cells.

scholarly journals Main Inflammatory Cells and Potentials of Anti-Inflammatory Agents in Prostate Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1153 ◽  
Author(s):  
Takuji Hayashi ◽  
Kazutoshi Fujita ◽  
Makoto Matsushita ◽  
Norio Nonomura
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Immune Cells ◽  
Acquired Resistance ◽  
Suppressor Cells ◽  
Basic Research ◽  
Inflammatory Cells ◽  
Intercellular Signaling ◽  
Prostate Cancer Progression ◽  
Anti Inflammatory

Prostate cancer is the most common type of cancer and the leading cause of cancer deaths among men in many countries. Preventing progression is a major concern for prostate cancer patients on active surveillance, patients with recurrence after radical therapies, and patients who acquired resistance to systemic therapies. Inflammation, which is induced by various factors such as infection, microbiome, obesity, and a high-fat diet, is the major etiology in the development of prostate cancer. Inflammatory cells play important roles in tumor progression. Various immune cells including tumor-associated neutrophils, tumor-infiltrating macrophages, myeloid-derived suppressor cells, and mast cells promote prostate cancer via various intercellular signaling. Further basic studies examining the relationship between the inflammatory process and prostate cancer progression are warranted. Interventions by medications and diets to control systemic and/or local inflammation might be effective therapies for prostate cancer progression. Epidemiological investigations and basic research using human immune cells or mouse models have revealed that non-steroidal anti-inflammatory drugs, metformin, statins, soy isoflavones, and other diets are potential interventions for preventing progression of prostate cancer by suppressing inflammation. It is essential to evaluate appropriate indications and doses of each drug and diet.

scholarly journals Chronic Inflammation in Non-Alcoholic Steatohepatitis: Molecular Mechanisms and Therapeutic Strategies

2020 ◽  
Vol 11 ◽  
Author(s):  
Carmelo Luci ◽  
Manon Bourinet ◽  
Pierre S. Leclère ◽  
Rodolphe Anty ◽  
Philippe Gual
Keyword(s):  
Endothelial Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Liver Sinusoidal Endothelial Cells ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Non-Alcoholic Steatohepatitis (NASH) is the progressive form of Non-Alcoholic Fatty Liver Disease (NAFLD), the main cause of chronic liver complications. The development of NASH is the consequence of aberrant activation of hepatic conventional immune, parenchymal, and endothelial cells in response to inflammatory mediators from the liver, adipose tissue, and gut. Hepatocytes, Kupffer cells and liver sinusoidal endothelial cells contribute to the significant accumulation of bone-marrow derived-macrophages and neutrophils in the liver, a hallmark of NASH. The aberrant activation of these immune cells elicits harmful inflammation and liver injury, leading to NASH progression. In this review, we highlight the processes triggering the recruitment and/or activation of hepatic innate immune cells, with a focus on macrophages, neutrophils, and innate lymphoid cells as well as the contribution of hepatocytes and endothelial cells in driving liver inflammation/fibrosis. On-going studies and preliminary results from global and specific therapeutic strategies to manage this NASH-related inflammation will also be discussed.

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