scholarly journals Role of Common-Gamma Chain Cytokines in NK Cell Development and Function: Perspectives for Immunotherapy

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Raffaella Meazza ◽  
Bruno Azzarone ◽  
Anna Maria Orengo ◽  
Silvano Ferrini
Keyword(s):  
Cell Biology ◽  
Defense Mechanism ◽  
Viral Infections ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Gamma Chain ◽  
Functional Activities ◽  
The Common ◽  
And Function

NK cells are components of the innate immunity system and play an important role as a first-line defense mechanism against viral infections and in tumor immune surveillance. Their development and their functional activities are controlled by several factors among which cytokines sharing the usage of the common cytokine-receptor gamma chain play a pivotal role. In particular, IL-2, IL-7, IL-15, and IL-21 are the members of this family predominantly involved in NK cell biology. In this paper, we will address their role in NK cell ontogeny, regulation of functional activities, development of specialized cell subsets, and acquisition of memory-like functions. Finally, the potential application of these cytokines as recombinant molecules to NK cell-based immunotherapy approaches will be discussed.

scholarly journals T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Kiekens ◽  
Wouter Van Loocke ◽  
Sylvie Taveirne ◽  
Sigrid Wahlen ◽  
Eva Persyn ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Nk Cell ◽  
Current Knowledge ◽  
Functional Differentiation ◽  
Cell Maturation ◽  
Hematopoietic Stem ◽  
And Function

T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.

scholarly journals Expression Regulation and Function of T-Bet in NK Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Chen Huang ◽  
Jiacheng Bi
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Immune Surveillance ◽  
T Box ◽  
Effector Functions ◽  
Mtorc1 Signaling ◽  
Ifn Γ ◽  
And Function ◽  
Innate Lymphocytes

Natural killer (NK) cells are cytotoxic innate lymphocytes that play an important role in immune surveillance. The development, maturation and effector functions of NK cells are orchestrated by the T-box transcription factor T-bet, whose expression is induced by cytokines such as IFN-γ, IL-12, IL-15 and IL-21 through the respective cytokine receptors and downstream JAK/STATs or PI3K-AKT-mTORC1 signaling pathways. In this review, we aim to discuss the expression and regulation of T-bet in NK cells, the role of T-bet in mouse NK cell development, maturation, and function, as well as the role of T-bet in acute, chronic infection, inflammation, autoimmune diseases and tumors.

scholarly journals Membrane-associated phase separation: organization and function emerge from a two-dimensional milieu

2021 ◽  
Author(s):  
Jonathon A Ditlev
Keyword(s):  
Phase Separation ◽  
Cell Biology ◽  
Cellular Environment ◽  
Condensate Formation ◽  
Associated Proteins ◽  
Available Technology ◽  
And Function ◽  
Surrounding Membrane

Abstract Liquid‒liquid phase separation (LLPS) of biomolecules has emerged as an important mechanism that contributes to cellular organization. Phase separated biomolecular condensates, or membrane-less organelles, are compartments composed of specific biomolecules without a surrounding membrane in the nucleus and cytoplasm. LLPS also occurs at membranes, where both lipids and membrane-associated proteins can de-mix to form phase separated compartments. Investigation of these membrane-associated condensates using in vitro biochemical reconstitution and cell biology has provided key insights into the role of phase separation in membrane domain formation and function. However, these studies have generally been limited by available technology to study LLPS on model membranes and the complex cellular environment that regulates condensate formation, composition, and function. Here, I briefly review our current understanding of membrane-associated condensates, establish why LLPS can be advantageous for certain membrane-associated condensates, and offer a perspective for how these condensates may be studied in the future.

Viruses Reveal the Secrets of Plasmodesmal Cell Biology

2020 ◽  
Vol 33 (1) ◽  
pp. 26-39 ◽  
Author(s):  
Brandon C. Reagan ◽  
Tessa M. Burch-Smith
Keyword(s):  
Cell Biology ◽  
Plant Viruses ◽  
Rna Molecules ◽  
Obligate Intracellular ◽  
Composition And Structure ◽  
Systemic Spread ◽  
Intercellular Movement ◽  
Virus Research ◽  
And Function

Plasmodesmata (PD) are essential for intercellular trafficking of molecules required for plant life, from small molecules like sugars and ions to macromolecules including proteins and RNA molecules that act as signals to regulate plant development and defense. As obligate intracellular pathogens, plant viruses have evolved to manipulate this communication system to facilitate the initial cell-to-cell and eventual systemic spread in their plant hosts. There has been considerable interest in how viruses manipulate the PD that connect the protoplasts of neighboring cells, and viruses have yielded invaluable tools for probing the structure and function of PD. With recent advances in biochemistry and imaging, we have gained new insights into the composition and structure of PD in the presence and absence of viruses. Here, we first discuss viral strategies for manipulating PD for their intercellular movement and examine how this has shed light on our understanding of native PD function. We then address the controversial role of the cytoskeleton in trafficking to and through PD. Finally, we address how viruses could alter PD structure and consider possible mechanisms of the phenomenon described as ‘gating’. This discussion supports the significance of virus research in elucidating the properties of PD, these persistently enigmatic plant organelles.

scholarly journals Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells

2019 ◽  
Vol 122 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Cong Hu ◽  
Bo Pang ◽  
Guangzhu Lin ◽  
Yu Zhen ◽  
Huanfa Yi
Keyword(s):  
Metabolic Pathways ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Metabolic Energy ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
And Function ◽  
Promote Tumour Development

AbstractIn recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.

scholarly journals Tumor-Related Exosomes Contribute to Tumor-Promoting Microenvironment: An Immunological Perspective

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Wuzhen Chen ◽  
Jingxin Jiang ◽  
Wenjie Xia ◽  
Jian Huang
Keyword(s):  
T Cell ◽  
Cell Activation ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Effector T Cell ◽  
T Cell Apoptosis ◽  
And Function

Exosomes are a kind of cell-released membrane-form structures which contain proteins, lipids, and nucleic acids. These vesicular organelles play a key role in intercellular communication. Numerous experiments demonstrated that tumor-related exosomes (TEXs) can induce immune surveillance in the microenvironment in vivo and in vitro. They can interfere with the maturation of DC cells, impair NK cell activation, induce myeloid-derived suppressor cells, and educate macrophages into protumor phenotype. They can also selectively induce effector T cell apoptosis via Fas/FasL interaction and enhance regulatory T cell proliferation and function by releasing TGF-β. In this review, we focus on the TEX-induced immunosuppression and microenvironment change. Based on the truth that TEXs play crucial roles in suppressing the immune system, studies on modification of exosomes as immunotherapy strategies will also be discussed.

scholarly journals Dysregulation of Natural Killer Cells in Obesity

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 573 ◽  
Author(s):  
Donal O’Shea ◽  
Andrew E. Hogan
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Cell Biology ◽  
Viral Infections ◽  
Nk Cell ◽  
Viral Immunity ◽  
Host Protection ◽  
Cell Functions ◽  
Innate Lymphocytes ◽  
The Impact

Natural killer (NK) cells are a population of lymphocytes which classically form part of the innate immune system. They are defined as innate lymphocytes, due to their ability to kill infected or transformed cells without prior activation. In addition to their cytotoxic abilities, NK cells are also rapid producers of inflammatory cytokines such as interferon gamma (IFN-γ) and are therefore a critical component of early immune responses. Due to these unique abilities, NK cells are a very important component of host protection, especially anti-tumour and anti-viral immunity. Obesity is a worldwide epidemic, with over 600 million adults and 124 million children now classified as obese. It is well established that individuals who are obese are at a higher risk of many acute and chronic conditions, including cancer and viral infections. Over the past 10 years, many studies have investigated the impact of obesity on NK cell biology, detailing systemic dysregulation of NK cell functions. More recently, several studies have investigated the role of NK cells in the homeostasis of adipose tissue and the pathophysiology of obesity. In this review, we will discuss in detail these studies and focus on emerging data detailing the metabolic mechanisms altering NK cells in obesity.

scholarly journals Role of high dose IV vitamin C and zinc in coronavirus

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Arooj Fatima ◽  
Muhammad Usman Ali Khan ◽  
Mehkaar Najeeb ◽  
Muhammad Yasoob Ali Khan ◽  
Faiz Ul Haq
Keyword(s):  
Vitamin C ◽  
Viral Infections ◽  
Physiological Activity ◽  
Symptomatic Treatment ◽  
Primary Treatment ◽  
High Dose ◽  
Global Pandemic ◽  
The Common ◽  
Taste And Smell

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome- related coronavirus 2 (SARS-CoV- 2), is now considered as an ongoing global pandemic. Common symptoms include pyrexia, cough, dyspnea, fatigue, sore throat, and loss of sense of taste and smell. Complications that can result from more severe insult on lung tissue is pneumonia and acute respiratory distress syndrome (ARDS), which can further lead to septic shock. It is also not uncommon to find neurological symptoms in patients suffering from COVID-19. The primary treatment for COVID-19 is symptomatic treatment and supportive care. As there is no known vaccination and antiviral therapy for this disease, there is a desperate need to find an alternative to control and stop the spread of disease. Maintaining adequate micronutrient balance might enhance the immunity and protect from viral infections as well. Vitamin C and zinc helps in improving symptoms and shortening the duration of the common cold. Vitamin C (L-ascorbic acid) possesses pleiotropic physiological activity. High dose Vitamin C has shown to be effective against the common flu, rhinovirus, avian virus, chikungunya, Zika, ARDS, and influenza, and there is evidence that supports the protective effect of high dose IV vitamin C during sepsis-induced ARDS due to COVID-19. Zinc has a profound impact on the replication of viruses. Increasing intracellular zinc concentration along with pyrithione (zinc ionophore) has been shown to impair the replication of several RNA viruses efficiently, including poliovirus, influenza virus and several picornaviruses. A combination of zinc and can also inhibit the replication of SARS-coronavirus in cell culture.

scholarly journals MiR-146a in Immunity and Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Nicole Rusca ◽  
Silvia Monticelli
Keyword(s):  
Immune Responses ◽  
Recent Progress ◽  
Viral Infections ◽  
Cellular Functions ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Different Types ◽  
A Cell ◽  
And Function

MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of the innate as well as adaptive immunity. Given its importance in regulating key cellular functions, it is not surprising that miR-146a expression was also found dysregulated in different types of tumors. In this paper, we summarize recent progress in understanding the role of miR-146a in innate and adaptive immune responses, as well as in disease.

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