scholarly journals Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Naveen Kumar ◽  
Pepijn Saraber ◽  
Zhangfan Ding ◽  
Anjali P. Kusumbe
Keyword(s):  
Immune Cell ◽  
Bone Cells ◽  
Cell Types ◽  
Bone Diseases ◽  
Whole Body ◽  
Skeletal System ◽  
Cell Production ◽  
Functionally Diverse ◽  
Bone Vasculature

The bones and joints in the skeletal system are composed of diverse cell types, including vascular niches, bone cells, connective tissue cells and mineral deposits and regulate whole-body homeostasis. The capacity of maintaining strength and generation of blood lineages lies within the skeletal system. Bone harbours blood and immune cells and their progenitors, and vascular cells provide several immune cell type niches. Blood vessels in bone are phenotypically and functionally diverse, with distinct capillary subtypes exhibiting striking changes with age. The bone vasculature has a special impact on osteogenesis and haematopoiesis, and dysregulation of the vasculature is associated with diverse blood and bone diseases. Ageing is associated with perturbed haematopoiesis, loss of osteogenesis, increased adipogenesis and diminished immune response and immune cell production. Endothelial and perivascular cells impact immune cell production and play a crucial role during inflammation. Here, we discuss normal and maladapted vascular niches in bone during development, homeostasis, ageing and bone diseases such as rheumatoid arthritis and osteoarthritis. Further, we discuss the role of vascular niches during bone malignancy.

scholarly journals Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

2013 ◽  
Vol 2013 ◽  
pp. 1-12
Author(s):  
Marisa Vulcano ◽  
María Gabriela Lombardi ◽  
María Elena Sales
Keyword(s):  
Dendritic Cells ◽  
Cholinergic System ◽  
Parasympathetic Nervous System ◽  
Immune Cell ◽  
Breast Tumors ◽  
Cell Types ◽  
Cellular Functions ◽  
And Migration ◽  
And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 810
Author(s):  
Camille Jacques ◽  
Robel Tesfaye ◽  
Melanie Lavaud ◽  
Steven Georges ◽  
Marc Baud’huin ◽  
...  
Keyword(s):  
Bone Cells ◽  
Osteoblastic Differentiation ◽  
Bone Diseases ◽  
Tumor Suppressor Protein ◽  
Genomic Integrity ◽  
Potential Implication ◽  
Cycle Arrest ◽  
Transcriptional Regulatory ◽  
Bone Sarcomas

The formation of the skeleton occurs throughout the lives of vertebrates and is achieved through the balanced activities of two kinds of specialized bone cells: the bone-forming osteoblasts and the bone-resorbing osteoclasts. Impairment in the remodeling processes dramatically hampers the proper healing of fractures and can also result in malignant bone diseases such as osteosarcoma. MicroRNAs (miRNAs) are a class of small non-coding single-strand RNAs implicated in the control of various cellular activities such as proliferation, differentiation, and apoptosis. Their post-transcriptional regulatory role confers on them inhibitory functions toward specific target mRNAs. As miRNAs are involved in the differentiation program of precursor cells, it is now well established that this class of molecules also influences bone formation by affecting osteoblastic differentiation and the fate of osteoblasts. In response to various cell signals, the tumor-suppressor protein p53 activates a huge range of genes, whose miRNAs promote genomic-integrity maintenance, cell-cycle arrest, cell senescence, and apoptosis. Here, we review the role of three p53-related miRNAs, miR-34c, -125b, and -203, in the bone-remodeling context and, in particular, in osteoblastic differentiation. The second aim of this study is to deal with the potential implication of these miRNAs in osteosarcoma development and progression.

Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness

1993 ◽  
Vol 264 (6) ◽  
pp. C1367-C1387 ◽  
Author(s):  
M. P. Blaustein
Keyword(s):  
Steady State ◽  
Cell Types ◽  
Whole Body ◽  
Cellular Mechanisms ◽  
Signaling Mechanism ◽  
Physiological Processes ◽  
Endogenous Ouabain ◽  
Adrenal Cortical Hormone ◽  
Salt And Water Balance

Ouabain is a well-known compound but a newly discovered adrenal cortical hormone that plays a role in cell Na+ regulation and in whole body salt and water balance. Ouabain may also be a paracrine hormone and may be secreted by some central nervous system neurons as well as by other types of cells. This article focuses on the cellular mechanisms that underlie the physiological (and pathophysiological) effects of ouabain. Ouabain directly inhibits the plasmalemmal Na+ pump in a variety of cell types. Low ouabain concentrations cause, in the steady state, a modest rise in the cytosolic Na+ concentration but only a minimal decline in membrane potential. All Na+ gradient-dependent processes may thereby be affected, albeit to only a small extent. Most important, however, is the secondary redistribution of Ca2+, mediated by Na(+)-Ca2+ exchange, that should slightly increase the cytosolic free Ca2+ concentration ([Ca2+]cyt). As a result of Ca2+ sequestration in intracellular stores [the endoplasmic and/or sarcoplasmic reticulum (ER/SR)], however, a new steady state is achieved with a slightly increased [Ca2+]cyt but a substantially augmented Ca2+ store; thus the ER/SR effectively acts as a Ca2+ amplifier. This extra stored Ca2+ is then available for mobilization whenever the cells are activated. Cytosolic Ca2+ is a key signaling mechanism in virtually all cells: it controls numerous physiological processes such as contraction, secretion, and excitability. Thus ouabain may modulate cell responsiveness via its influence on ER/SR Ca2+ stores. With these principles in mind, we examine evidence that endogenous ouabain may play a role in numerous physiological and pathophysiological processes associated with altered fluid and electrolyte metabolism and deviations from the normal blood pressure-blood volume relationship. We discuss the possible participation of ouabain in the regulation of vascular tone and then consider the putative role of ouabain in several forms of hypertension, congestive heart failure, thyroid and adrenocortical dysfunction, and diabetes mellitus, as well as in the adaptation to high altitude.

scholarly journals Homogentisic acid-derived pigment as a biocompatible label for optoacoustic imaging of macrophages

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ina Weidenfeld ◽  
Christian Zakian ◽  
Peter Duewell ◽  
Andriy Chmyrov ◽  
Uwe Klemm ◽  
...  
Keyword(s):  
Single Cells ◽  
Cell Types ◽  
Homogentisic Acid ◽  
Tissue Imaging ◽  
Whole Body ◽  
Whole Body Imaging ◽  
Optoacoustic Imaging ◽  
Pigment Formation ◽  
Functionally Diverse

Abstract Macrophages are one of the most functionally-diverse cell types with roles in innate immunity, homeostasis and disease making them attractive targets for diagnostics and therapy. Photo- or optoacoustics could provide non-invasive, deep tissue imaging with high resolution and allow to visualize the spatiotemporal distribution of macrophages in vivo. However, present macrophage labels focus on synthetic nanomaterials, frequently limiting their ability to combine both host cell viability and functionality with strong signal generation. Here, we present a homogentisic acid-derived pigment (HDP) for biocompatible intracellular labeling of macrophages with strong optoacoustic contrast efficient enough to resolve single cells against a strong blood background. We study pigment formation during macrophage differentiation and activation, and utilize this labeling method to track migration of pro-inflammatory macrophages in vivo with whole-body imaging. We expand the sparse palette of macrophage labels for in vivo optoacoustic imaging and facilitate research on macrophage functionality and behavior.

Chemokines in Oral Inflammatory Diseases: Apical Periodontitis and Periodontal Disease

2007 ◽  
Vol 86 (4) ◽  
pp. 306-319 ◽  
Author(s):  
T.A. Silva ◽  
G.P. Garlet ◽  
S.Y. Fukada ◽  
J.S. Silva ◽  
F.Q. Cunha
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Bone Cells ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Cellular Responses ◽  
Experimental Models ◽  
Periodontal Tissue ◽  
Oral Diseases ◽  
Specific Receptors

The inflammatory oral diseases are characterized by the persistent migration of polymorphonuclear leukocytes, monocytes, lymphocytes, plasma and mast cells, and osteoblasts and osteoclasts. In the last decade, there has been a great interest in the mediators responsible for the selective recruitment and activation of these cell types at inflammatory sites. Of these mediators, the chemokines have received particular attention in recent years. Chemokine messages are decoded by specific receptors that initiate signal transduction events, leading to a multitude of cellular responses, including chemotaxis and activation of inflammatory and bone cells. However, little is known about their role in the pathogenesis of inflammatory oral diseases. The purpose of this review is to summarize the findings regarding the role of chemokines in periapical and periodontal tissue inflammation, and the integration, into experimental models, of the information about the role of chemokines in human diseases.

scholarly journals Serotonin Pathway in Neuroimmune Network

2021 ◽  
Author(s):  
Giada Mondanelli ◽  
Claudia Volpi
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Signalling Molecules ◽  
Functional Interactions ◽  
Neuroimmune System ◽  
Neurologic Disorders ◽  
The Central Nervous System ◽  
Specific Receptors ◽  
Serotonin Pathway

Once considered merely as a neurotransmitter, serotonin (5-HT) now enjoys a renewed reputation as an interlocutor in the dense and continuous dialogue between neuroendocrine and immune systems. In the last decades, a role has been depicted for serotonin and its derivatives as modulators of several immunological events, due to the expression of specific receptors or enzymes controlling 5-HT metabolism in diverse immune cell types. A growing body of evidence suggests that the effects of molecules belonging to the 5-HT pathways on the neuroimmune communication may be relevant in the clinical outcome of autoimmune/inflammatory pathologies of the central nervous system (CNS), such as multiple sclerosis, but also in Alzheimer’s disease, or in mood disorders and major depression. Moreover, since the predominance of 5-HT is produced by enterochromaffin cells of the gastrointestinal tract, where 5-HT and its derivatives are important mucosal signalling molecules giving rise to the so-called “brain-gut axis”, alterations in brain-gut communication are also involved in the pathogenesis and pathophysiology of several psychiatric and neurologic disorders. Here we illustrate how functional interactions between immune and neuronal cells are crucial to orchestrate tissue homeostasis and integrity, and the role of serotonin pathway components as pillars of the neuroimmune system.

scholarly journals Role of Immune Cell-Specific Hypermethylation Signatures in Classification and Risk Stratification of Breast Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Yong Chen ◽  
Fada Xia ◽  
Bo Jiang ◽  
Wenlong Wang ◽  
Xinying Li
Keyword(s):  
Breast Cancer ◽  
Risk Stratification ◽  
Immune Cells ◽  
Prediction Accuracy ◽  
Prognostic Value ◽  
Clinical Characteristics ◽  
Immune Cell ◽  
Cell Types ◽  
Clinical Model

Background: Epigenetic regulation, including DNA methylation, plays a major role in shaping the identity and function of immune cells. Innate and adaptive immune cells recruited into tumor tissues contribute to the formation of the tumor immune microenvironment (TIME), which is closely involved in tumor progression in breast cancer (BC). However, the specific methylation signatures of immune cells have not been thoroughly investigated yet. Additionally, it remains unknown whether immune cells-specific methylation signatures can identify subgroups and stratify the prognosis of BC patients.Methods: DNA methylation profiles of six immune cell types from eight datasets downloaded from the Gene Expression Omnibus were collected to identify immune cell-specific hypermethylation signatures (IC-SHMSs). Univariate and multivariate cox regression analyses were performed using BC data obtained from The Cancer Genome Atlas to identify the prognostic value of these IC-SHMSs. An unsupervised clustering analysis of the IC-SHMSs with prognostic value was performed to categorize BC patients into subgroups. Multiple Cox proportional hazard models were constructed to explore the role of IC-SHMSs and their relationship to clinical characteristics in the risk stratification of BC patients. Integrated discrimination improvement (IDI) was performed to determine whether the improvement of IC-SHMSs on clinical characteristics in risk stratification was statistically significant.Results: A total of 655 IC-SHMSs of six immune cell types were identified. Thirty of them had prognostic value, and 10 showed independent prognostic value. Four subgroups of BC patients, which showed significant heterogeneity in terms of survival prognosis and immune landscape, were identified. The model incorporating nine IC-SHMSs showed similar survival prediction accuracy as the clinical model incorporating age and TNM stage [3-year area under the curve (AUC): 0.793 vs. 0.785; 5-year AUC: 0.735 vs. 0.761]. Adding the IC-SHMSs to the clinical model significantly improved its prediction accuracy in risk stratification (3-year AUC: 0.897; 5-year AUC: 0.856). The results of IDI validated the statistical significance of the improvement (p < 0.05).Conclusions: Our study suggests that IC-SHMSs may serve as signatures of classification and risk stratification in BC. Our findings provide new insights into epigenetic signatures, which may help improve subgroup identification, risk stratification, and treatment management.

scholarly journals 67 Immunometabolism – emerging concepts and potential applications in livestock

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 101-101
Author(s):  
Barry J Bradford
Keyword(s):  
Immune System ◽  
Communication Networks ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Whole Body ◽  
Phagocytic Cells ◽  
Adaptive Immune Cells ◽  
Potential Applications ◽  
Host Microbe Interactions

Abstract Our understanding of the immune system emerged from the study of disease processes and the communication networks used by various cell types to respond to pathogens. As with many aspects of physiology, this initial view was colored by the techniques available at the time. With technical advances beginning in the 1990, research in sepsis and obesity began to identify critical interactions between the immune system and metabolism. Our current understanding of these interactions is informed by two active but largely distinct research communities. Many in the field of immunology are utilizing cellular metabolism tools to understand mitochondrial function and fuel use in response to activation of innate and adaptive immune cells, especially as these relate to cancer. From another vantage point, many metabolic physiologists are now seeking to understand the importance of tissue-resident immune cells and immune signaling molecules in metabolic homeostasis and pathologies. Beyond human health implications of recent findings, a number of immunometabolism insights have informed our understanding of livestock health. In inflammatory events, phagocytic cells are activated, and the dramatic increase in oxidative metabolism is driven primarily by glucose use. Metabolism of healthy animals is also influenced by secretions from immune cells. Studies in mice indicate that appropriate host/microbe interactions (balancing protection and tolerance) are mediated by a network of immune cell types in the gut, which is critical to both absorptive and barrier functions of the gut. Adipose tissue immune cells regulate lipolytic rate, insulin sensitivity, and perhaps whole-body inflammatory tone. Local immune cell impacts on metabolism of other organs, including the liver and pancreas, are also emerging. Immunity and metabolism are tightly interwoven, and the evolving understanding of these links may enable nutritional or pharmacological strategies to enhance resilience to disease and alter nutrient partitioning in livestock.

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