scholarly journals Non-genetic Heterogeneity of Macrophages in Diseases—A Medical Perspective

2020 ◽  
Vol 8 ◽  
Author(s):  
Grégoire Gessain ◽  
Camille Blériot ◽  
Florent Ginhoux
Keyword(s):  
Genetic Heterogeneity ◽  
Immune Cells ◽  
Therapeutic Strategies ◽  
Functional Plasticity ◽  
Comprehensive Overview ◽  
Metabolic Functions ◽  
Age Related ◽  
Neoplastic Disorders ◽  
Medical Perspective ◽  
Uniform Population

Macrophages are sessile immune cells with a high functional plasticity. Initially considered as a uniform population of phagocytic scavengers, it is now widely accepted that these cells also assume developmental and metabolic functions specific of their tissue of residence. Hence, the paradigm is shifting while our comprehension of macrophage heterogeneity improves. Accordingly, exploiting this intrinsic versatility appears more and more promising for the establishment of innovative therapeutic strategies. Nevertheless, identifying relevant therapeutic targets remains a considerable challenge. Herein, we discuss various features of macrophage heterogeneity in five main categories of human diseases: infectious, inflammatory, metabolic, age-related, and neoplastic disorders. We summarize the current understanding of how macrophage heterogeneity may impact the pathogenesis of these diseases and propose a comprehensive overview with the aim to help in establishing future macrophage-targeted therapies.

scholarly journals The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 485
Author(s):  
Lorenzo Cuollo ◽  
Fabrizio Antonangeli ◽  
Angela Santoni ◽  
Alessandra Soriani
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Senescent Cell ◽  
Pharmacological Intervention ◽  
Tissue Microenvironment ◽  
Age Related ◽  
Secretory Phenotype ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.

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 Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

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.

scholarly journals Aging and age‐related diseases: from mechanisms to therapeutic strategies

2021 ◽  
Author(s):  
Zhe Li ◽  
Zhenkun Zhang ◽  
Yikun Ren ◽  
Yingying Wang ◽  
Jiarui Fang ◽  
...  
Keyword(s):  
Therapeutic Strategies ◽  
Age Related

The Intersection of Metformin and Inflammation

2021 ◽  
Author(s):  
Leena P. Bharath ◽  
Barbara S. Nikolajczyk
Keyword(s):  
Mitochondrial Function ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Types ◽  
Remarkable Effect ◽  
Tumor Onset ◽  
Age Related ◽  
Immune Mediated ◽  
Autoimmune Conditions ◽  
Near Term

The biguanide metformin is the most commonly used antidiabetic drug. Recent studies show that metformin not only improves chronic inflammation by improving metabolic parameters but also has a direct anti-inflammatory effect. In light of these findings, it is essential to identify the inflammatory pathways targeted by metformin to develop a comprehensive understanding of the mechanisms of action of this drug. Commonly accepted mechanisms of metformin action include AMPK activation and inhibition of mTOR pathways, which are evaluated in multiple diseases. Additionally, metformin's action on mitochondrial function and cellular homeostasis processes such as autophagy, is of particular interest because of the importance of these mechanisms in maintaining cellular health. Both dysregulated mitochondria and failure of the autophagy pathways, the latter of which impair clearance of dysfunctional, damaged, or excess organelles, affect cellular health drastically and can trigger the onset of metabolic and age-related diseases. Immune cells are the fundamental cell types that govern the health of an organism. Thus, dysregulation of autophagy or mitochondrial function in immune cells has a remarkable effect on susceptibility to infections, response to vaccination, tumor onset, and the development of inflammatory and autoimmune conditions. Here we summarize the latest research on metformin's regulation of immune cell mitochondrial function and autophagy as evidence that new clinical trials on metformin with primary outcomes related to the immune system should be considered to treat immune-mediated diseases over the near term.

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.

scholarly journals The Complex Role of Regulatory T Cells in Immunity and Aging

2021 ◽  
Vol 11 ◽  
Author(s):  
Lourdes Rocamora-Reverte ◽  
Franz Leonard Melzer ◽  
Reinhard Würzner ◽  
Birgit Weinberger
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Γδt Cells ◽  
Cell Functions ◽  
Age Related ◽  
Self Antigens

The immune system is a tightly regulated network which allows the development of defense mechanisms against foreign antigens and tolerance toward self-antigens. Regulatory T cells (Treg) contribute to immune homeostasis by maintaining unresponsiveness to self-antigens and suppressing exaggerated immune responses. Dysregulation of any of these processes can lead to serious consequences. Classically, Treg cell functions have been described in CD4+ T cells, but other immune cells also harbour the capacity to modulate immune responses. Regulatory functions have been described for different CD8+ T cell subsets, as well as other T cells such as γδT cells or NKT cells. In this review we describe the diverse populations of Treg cells and their role in different scenarios. Special attention is paid to the aging process, which is characterized by an altered composition of immune cells. Treg cells can contribute to the development of various age-related diseases but they are poorly characterized in aged individuals. The huge diversity of cells that display immune modulatory functions and the lack of universal markers to identify Treg make the expanding field of Treg research complex and challenging. There are still many open questions that need to be answered to solve the enigma of regulatory T cells.

scholarly journals The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective

2019 ◽  
Vol 77 (5) ◽  
pp. 819-833 ◽  
Author(s):  
Parviz Mammadzada ◽  
Pablo M. Corredoira ◽  
Helder André
Keyword(s):  
Gene Therapy ◽  
Macular Degeneration ◽  
Clinical Phenotype ◽  
Therapeutic Strategies ◽  
Age Related Macular Degeneration ◽  
Hypoxia Inducible Factors ◽  
Ocular Angiogenesis ◽  
Gene Therapies ◽  
Age Related

AbstractUnderstanding the mechanisms that underlie age-related macular degeneration (AMD) has led to the identification of key molecules. Hypoxia-inducible transcription factors (HIFs) have been associated with choroidal neovascularization and the progression of AMD into the neovascular clinical phenotype (nAMD). HIFs regulate the expression of multiple growth factors and cytokines involved in angiogenesis and inflammation, hallmarks of nAMD. This knowledge has propelled the development of a new group of therapeutic strategies focused on gene therapy. The present review provides an update on current gene therapies in ocular angiogenesis, particularly nAMD, from both basic and clinical perspectives.

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