scholarly journals Hypoxia-inducible factors in T lymphocyte differentiation and function. A Review in the Theme: Cellular Responses to Hypoxia

2015 ◽  
Vol 309 (9) ◽  
pp. C580-C589 ◽  
Author(s):  
Jin-Hui Tao ◽  
Joseph Barbi ◽  
Fan Pan
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Fine Tuning ◽  
Proper Function ◽  
Hypoxia Inducible Factors ◽  
Low Oxygen ◽  
Innate And Adaptive Immunity ◽  
And Function ◽  
Shed Light ◽  
Made In

Low oxygen concentrations or hypoxia is a trait common to inflamed tissues. Therefore it is not surprising that pathways of hypoxic stress response, largely governed by hypoxia-inducible factors (HIF), are highly relevant to the proper function of immune cells. HIF expression and stabilization in immune cells can be triggered not only by hypoxia, but also by a variety of stimuli and pathological stresses associated with leukocyte activation and inflammation. In addition to its role as a sensor of oxygen scarcity, HIF is also a major regulator of immune cell metabolic function. Rapid progress is being made in elucidating the roles played by HIF in diverse aspects of both innate and adaptive immunity. Here we discuss a number of breakthroughs that have shed light on how HIF expression and activity impact the differentiation and function of diverse T cell populations. The insights gained from these findings may serve as the foundation for future therapies aimed at fine-tuning the immune response.

scholarly journals When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Katrin Schlie ◽  
Jaeline E. Spowart ◽  
Luke R. K. Hughson ◽  
Katelin N. Townsend ◽  
Julian J. Lum
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Patient Treatment ◽  
Low Oxygen ◽  
Tumor Environment ◽  
And Function ◽  
The Impact

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism. Autophagy upregulation in cancer cells liberates nutrients, decreases the buildup of reactive oxygen species, and aids in the clearance of misfolded proteins. Together, these features impart a survival advantage for cancer cells in the tumor microenvironment. This observation has led to intense research efforts focused on developing autophagy-modulating drugs for cancer patient treatment. However, other cells that infiltrate the tumor environment such as immune cells also encounter hypoxia likely resulting in hypoxia-induced autophagy. In light of the fact that autophagy is crucial for immune cell proliferation as well as their effector functions such as antigen presentation and T cell-mediated killing of tumor cells, anticancer treatment strategies based on autophagy modulation will need to consider the impact of autophagy on the immune system.

scholarly journals Immunometabolism in the Tumor Microenvironment

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Dominic G. Roy ◽  
Irem Kaymak ◽  
Kelsey S. Williams ◽  
Eric H. Ma ◽  
Russell G. Jones
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Cancer Biology ◽  
Antitumor Immunity ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Proper Function ◽  
Annual Review ◽  
Publication Date ◽  
And Function

Advances in immunotherapy have underscored the importance of antitumor immune responses in controlling cancer. However, the tumor microenvironment (TME) imposes several obstacles to the proper function of immune cells, including a metabolically challenging and immunosuppressive microenvironment. The increased metabolic activity of tumor cells can lead to the depletion of key nutrients required by immune cells and the accumulation of byproducts that hamper antitumor immunity. Furthermore, the presence of suppressive immune cells, such as regulatory T cells and myeloid-derived suppressor cells, and the expression of immune inhibitory receptors can negatively impact immune cell metabolism and function. This review summarizes the metabolic reprogramming that is characteristic of various immune cell subsets, discusses how the metabolism and function of immune cells is shaped by the TME, and highlights how therapeutic interventions aimed at improving the metabolic fitness of immune cells and alleviating the metabolic constraints in the TME can boost antitumor immunity. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals How Changes in the Nutritional Landscape Shape Gut Immunometabolism

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 823
Author(s):  
Jian Tan ◽  
Duan Ni ◽  
Rosilene V. Ribeiro ◽  
Gabriela V. Pinget ◽  
Laurence Macia
Keyword(s):  
Immune Cells ◽  
Metabolic Pathways ◽  
Immune Cell ◽  
Food Additives ◽  
Cell Activity ◽  
Inflammatory Cells ◽  
Therapeutic Approaches ◽  
Food Antigens ◽  
And Function ◽  
Micro Organisms

Cell survival, proliferation and function are energy-demanding processes, fuelled by different metabolic pathways. Immune cells like any other cells will adapt their energy production to their function with specific metabolic pathways characteristic of resting, inflammatory or anti-inflammatory cells. This concept of immunometabolism is revolutionising the field of immunology, opening the gates for novel therapeutic approaches aimed at altering immune responses through immune metabolic manipulations. The first part of this review will give an extensive overview on the metabolic pathways used by immune cells. Diet is a major source of energy, providing substrates to fuel these different metabolic pathways. Protein, lipid and carbohydrate composition as well as food additives can thus shape the immune response particularly in the gut, the first immune point of contact with food antigens and gastrointestinal tract pathogens. How diet composition might affect gut immunometabolism and its impact on diseases will also be discussed. Finally, the food ingested by the host is also a source of energy for the micro-organisms inhabiting the gut lumen particularly in the colon. The by-products released through the processing of specific nutrients by gut bacteria also influence immune cell activity and differentiation. How bacterial metabolites influence gut immunometabolism will be covered in the third part of this review. This notion of immunometabolism and immune function is recent and a deeper understanding of how lifestyle might influence gut immunometabolism is key to prevent or treat diseases.

scholarly journals Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens

Gut ◽  
2017 ◽  
Vol 67 (5) ◽  
pp. 847-859 ◽  
Author(s):  
Allison Cabinian ◽  
Daniel Sinsimer ◽  
May Tang ◽  
Youngsoon Jang ◽  
Bongkum Choi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Cells ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Premature Death ◽  
Enteric Pathogens ◽  
Immune Protection ◽  
Intestinal Immunity ◽  
Cell Responses ◽  
And Function

BackgroundInteractions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field.AimWe have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is.MethodsExpression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium.ResultsSLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC)TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death.ConclusionsSLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.

scholarly journals Single cell analysis reveals immune cell–adipocyte crosstalk regulating the transcription of thermogenic adipocytes

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Prashant Rajbhandari ◽  
Douglas Arneson ◽  
Sydney K Hart ◽  
In Sook Ahn ◽  
Graciel Diamante ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cells ◽  
Immune Cell ◽  
Single Cell Analysis ◽  
Metabolic Response ◽  
Cell Types ◽  
Specific Cell ◽  
Beneficial Effects ◽  
Thermogenic Adipocytes ◽  
And Function

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.

scholarly journals Neuroimmune Semaphorin 4A in Cancer Angiogenesis and Inflammation: A Promoter or a Suppressor?

2018 ◽  
Vol 20 (1) ◽  
pp. 124 ◽  
Author(s):  
Apoorva Iyer ◽  
Svetlana Chapoval
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Fine Tuning ◽  
Breast Cancers ◽  
Immune Functions ◽  
Immune Cell Activation ◽  
Important Regulator ◽  
And Function ◽  
Axon Guidance Molecule ◽  
Guidance Molecule

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function, instructing a fine tuning of the immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal, and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro- or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

scholarly journals Long Noncoding RNA in Myeloid and Lymphoid Cell Differentiation, Polarization and Function

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 269 ◽  
Author(s):  
Imran Ahmad ◽  
Araceli Valverde ◽  
Fayek Ahmad ◽  
Afsar Raza Naqvi
Keyword(s):  
Cell Differentiation ◽  
Immune Cells ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Immune Cell ◽  
Lymphoid Cells ◽  
Tissue Cell ◽  
Specific Expression ◽  
And Function

Long noncoding RNA (lncRNA) are a class of endogenous, non-protein coding RNAs that are increasingly being associated with various cellular functions and diseases. Yet, despite their ubiquity and abundance, only a minute fraction of these molecules has an assigned function. LncRNAs show tissue-, cell-, and developmental stage-specific expression, and are differentially expressed under physiological or pathological conditions. The role of lncRNAs in the lineage commitment of immune cells and shaping immune responses is becoming evident. Myeloid cells and lymphoid cells are two major classes of immune systems that work in concert to initiate and amplify innate and adaptive immunity in vertebrates. In this review, we provide mechanistic roles of lncRNA through which these noncoding RNAs can directly participate in the differentiation, polarization, and activation of myeloid (monocyte, macrophage, and dendritic cells) and lymphoid cells (T cells, B cells, and NK cells). While our knowledge on the role of lncRNA in immune cell differentiation and function has improved in the past decade, further studies are required to unravel the biological role of lncRNAs and identify novel mechanisms of lncRNA functions in immune cells. Harnessing the regulatory potential of lncRNAs can provide novel diagnostic and therapeutic targets in treating immune cell related diseases.

scholarly journals Immunometabolism at the Nexus of Cancer Therapeutic Efficacy and Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Javier Traba ◽  
Michael N. Sack ◽  
Thomas A. Waldmann ◽  
Olga M. Anton
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Metabolism ◽  
Immune Surveillance ◽  
Antitumor Effects ◽  
Cancer Management ◽  
Immunosuppressive Tumor Microenvironment ◽  
And Function ◽  
Main Effects

Constitutive activity of the immune surveillance system detects and kills cancerous cells, although many cancers have developed strategies to avoid detection and to resist their destruction. Cancer immunotherapy entails the manipulation of components of the endogenous immune system as targeted approaches to control and destroy cancer cells. Since one of the major limitations for the antitumor activity of immune cells is the immunosuppressive tumor microenvironment (TME), boosting the immune system to overcome the inhibition provided by the TME is a critical component of oncotherapeutics. In this article, we discuss the main effects of the TME on the metabolism and function of immune cells, and review emerging strategies to potentiate immune cell metabolism to promote antitumor effects either as monotherapeutics or in combination with conventional chemotherapy to optimize cancer management.

scholarly journals THERAPEUTIC TARGETING OF HYPOXIA-INDUCIBLE FACTOR SIGNALING PATHWAYS- A PROMISING APPROACH IN CANCER TREATMENT

2020 ◽  
Vol 8 (9) ◽  
pp. 1332-1337
Author(s):  
Anjum Mohammad Shaik ◽  
◽  
Valli Harisomayajula ◽  
Saranya M.L ◽  
Phani Greeshma Veeramachaneni ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Immune Cells ◽  
Cell Cycle Regulation ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factors ◽  
Low Oxygen ◽  
Therapeutic Targeting ◽  
Expression Of Genes ◽  
Transcription Regulators ◽  
Cycle Regulation

Oxygen and nutrients are delivered to the cells with the help of the vascular networking system, which makes availability of oxygen as primary regulator for many processes. Low oxygen availability condition activates the Hypoxia Inducible Factors (HIF), which are transcription regulators helping in the expression of genes related to cell cycle regulation and angiogenesis. HIF is hence regarded as the master regulator of angiogenesis. The oxygen deprival is due to the increased consumption of oxygen in the tumor microenvironment and in turn leads to hypoxia. A thorough understanding of how hypoxia influences angiogenesis mediated by several pathways has become essential for identifying novel strategies targeting HIF thereby blocking angiogenesis. In this review we would discuss about the HIF signaling pathways and altered functions of immune cells due to hypoxia by considering that reducing or targeting hypoxia may in turn prevent the suppression of anti-tumor immune response.

scholarly journals Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Pankaj Dipankar ◽  
Puneet Kumar ◽  
Shiba Prasad Dash ◽  
Pranita P. Sarangi
Keyword(s):  
Cell Migration ◽  
Immune Cells ◽  
Rho Gtpases ◽  
Inflammatory Cell ◽  
Immune Cell ◽  
Rho Gtpase ◽  
Innate Immune ◽  
Molecular Organization ◽  
Exchange Reactions ◽  
And Function

Systematic regulation of leukocyte migration to the site of infection is a vital step during immunological responses. Improper migration and localization of immune cells could be associated with disease pathology as seen in systemic inflammation. Rho GTPases act as molecular switches during inflammatory cell migration by cycling between Rho-GDP (inactive) to Rho-GTP (active) forms and play an essential role in the precise regulation of actin cytoskeletal dynamics as well as other immunological functions of leukocytes. Available reports suggest that the dysregulation of Rho GTPase signaling is associated with various inflammatory diseases ranging from mild to life-threatening conditions. Therefore, it is crucial to understand the step-by-step activation and inactivation of GTPases and the functioning of different Guanine Nucleotide Exchange Factors (GEFs) and GTPase-Activating Proteins (GAPs) that regulate the conversion of GDP to GTP and GTP to GDP exchange reactions, respectively. Here, we describe the molecular organization and activation of various domains of crucial elements associated with the activation of Rho GTPases using solved PDB structures. We will also present the latest evidence available on the relevance of Rho GTPases in the migration and function of innate immune cells during inflammation. This knowledge will help scientists design promising drug candidates against the Rho-GTPase-centric regulatory molecules regulating inflammatory cell migration.

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