scholarly journals Molecular Chaperones: Molecular Assembly Line Brings Metabolism and Immunity in Shape

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 394
Author(s):  
Haoxin Zhao ◽  
Lydia N. Raines ◽  
Stanley Ching-Cheng Huang

Molecular chaperones are a set of conserved proteins that have evolved to assist the folding of many newly synthesized proteins by preventing their misfolding under conditions such as elevated temperatures, hypoxia, acidosis and nutrient deprivation. Molecular chaperones belong to the heat shock protein (HSP) family. They have been identified as important participants in immune functions including antigen presentation, immunostimulation and immunomodulation, and play crucial roles in metabolic rewiring and epigenetic circuits. Growing evidence has accumulated to indicate that metabolic pathways and their metabolites influence the function of immune cells and can alter transcriptional activity through epigenetic modification of (de)methylation and (de)acetylation. However, whether molecular chaperones can regulate metabolic programs to influence immune activity is still largely unclear. In this review, we discuss the available data on the biological function of molecular chaperones to immune responses during inflammation, with a specific focus on the interplay between molecular chaperones and metabolic pathways that drive immune cell fate and function.

Author(s):  
Adrià-Arnau Martí i Líndez ◽  
Walter Reith

AbstractA growing body of evidence indicates that, over the course of evolution of the immune system, arginine has been selected as a node for the regulation of immune responses. An appropriate supply of arginine has long been associated with the improvement of immune responses. In addition to being a building block for protein synthesis, arginine serves as a substrate for distinct metabolic pathways that profoundly affect immune cell biology; especially macrophage, dendritic cell and T cell immunobiology. Arginine availability, synthesis, and catabolism are highly interrelated aspects of immune responses and their fine-tuning can dictate divergent pro-inflammatory or anti-inflammatory immune outcomes. Here, we review the organismal pathways of arginine metabolism in humans and rodents, as essential modulators of the availability of this semi-essential amino acid for immune cells. We subsequently review well-established and novel findings on the functional impact of arginine biosynthetic and catabolic pathways on the main immune cell lineages. Finally, as arginine has emerged as a molecule impacting on a plethora of immune functions, we integrate key notions on how the disruption or perversion of arginine metabolism is implicated in pathologies ranging from infectious diseases to autoimmunity and cancer.


Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 80
Author(s):  
Joohwan Kim ◽  
Gina Lee

Nutrients and metabolic pathways regulate cell growth and cell fate decisions via epigenetic modification of DNA and histones. Another key genetic material, RNA, also contains diverse chemical modifications. Among these, N6-methyladenosine (m6A) is the most prevalent and evolutionarily conserved RNA modification. It functions in various aspects of developmental and disease states, by controlling RNA metabolism, such as stability and translation. Similar to other epigenetic processes, m6A modification is regulated by specific enzymes, including writers (methyltransferases), erasers (demethylases), and readers (m6A-binding proteins). As this is a reversible enzymatic process, metabolites can directly influence the flux of this reaction by serving as substrates and/or allosteric regulators. In this review, we will discuss recent understanding of the regulation of m6A RNA modification by metabolites, nutrients, and cellular metabolic pathways.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 823
Author(s):  
Jian Tan ◽  
Duan Ni ◽  
Rosilene V. Ribeiro ◽  
Gabriela V. Pinget ◽  
Laurence Macia

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.


BioEssays ◽  
2020 ◽  
pp. 2000067
Author(s):  
Marcela Hortová‐Kohoutková ◽  
Petra Lázničková ◽  
Jan Frič

2018 ◽  
Vol 20 (1) ◽  
pp. 124 ◽  
Author(s):  
Apoorva Iyer ◽  
Svetlana Chapoval

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.


2006 ◽  
Vol 85 (12) ◽  
pp. 1061-1073 ◽  
Author(s):  
A. Jewett ◽  
C. Head ◽  
N.A. Cacalano

Mounting effective anti-tumor immune responses against tumors by both the innate and adaptive immune effectors is important for the clearance of tumors. However, accumulated evidence indicates that immune responses that should otherwise suppress or eliminate transformed cells are themselves suppressed by the function of tumor cells in a variety of cancer patients, including those with oral cancers. Signaling abnormalities, spontaneous apoptosis, and reduced proliferation and function of circulating natural killer cells (NK), T-cells, dendritic cells (DC), and tumor-infiltrating lymphocytes (TILs) have been documented previously in oral cancer patients. Several mechanisms have been proposed for the functional deficiencies of tumor-associated immune cells in oral cancer patients. Both soluble factors and contact-mediated immunosuppression by the tumor cells have been implicated in the inhibition of immune cell function and the progression of tumors. More recently, elevated levels and function of key transcription factors in tumor cells, particularly NFκB and STAT3, have been shown to mediate immune suppression in the tumor microenvironment. This review will focus on these emerging mechanisms of immunosuppression in oral cancers.


Aging Cell ◽  
2016 ◽  
Vol 15 (3) ◽  
pp. 400-406 ◽  
Author(s):  
Rita Vicente ◽  
Anne-Laure Mausset-Bonnefont ◽  
Christian Jorgensen ◽  
Pascale Louis-Plence ◽  
Jean-Marc Brondello

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5651
Author(s):  
Eleftheria Papaioannou ◽  
María del Pilar González-Molina ◽  
Ana M. Prieto-Muñoz ◽  
Laura Gámez-Reche ◽  
Alicia González-Martín

Cancer immunology research has mainly focused on the role of protein-coding genes in regulating immune responses to tumors. However, despite more than 70% of the human genome is transcribed, less than 2% encodes proteins. Many non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been identified as critical regulators of immune cell development and function, suggesting that they might play important roles in orchestrating immune responses against tumors. In this review, we summarize the scientific advances on the role of ncRNAs in regulating adaptive tumor immunity, and discuss their potential therapeutic value in the context of cancer immunotherapy.


2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Inga Wessels ◽  
Henrike Josephine Fischer ◽  
Lothar Rink

Evidence for the importance of zinc for all immune cells and for mounting an efficient and balanced immune response to various environmental stressors has been accumulating in recent years. This article describes the role of zinc in fundamental biological processes and summarizes our current knowledge of zinc's effect on hematopoiesis, including differentiation into immune cell subtypes. In addition, the important role of zinc during activation and function of immune cells is detailed and associated with the specific immune responses to bacteria, parasites, and viruses. The association of zinc with autoimmune reactions and cancers as diseases with increased or decreased immune responses is also discussed. This article provides a broad overview of the manifold roles that zinc, or its deficiency, plays in physiology and during various diseases. Consequently, we discuss why zinc supplementation should be considered, especially for people at risk of deficiency. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


ILAR Journal ◽  
2018 ◽  
Vol 59 (3) ◽  
pp. 309-322
Author(s):  
Signe Tandrup Schmidt ◽  
Gabriel Kristian Pedersen ◽  
Dennis Christensen

Abstract Many different adjuvants are currently being developed for subunit vaccines against a number of pathogens and diseases. Rational design is increasingly used to develop novel vaccine adjuvants, which requires extensive knowledge of, for example, the desired immune responses, target antigen-presenting cell subsets, their localization, and expression of relevant pattern-recognition receptors. The adjuvant mechanism of action and efficacy are usually evaluated in animal models, where mice are by far the most used. In this review, we present methods for assessing adjuvant efficacy and function in animal models: (1) whole-body biodistribution evaluated by using fluorescently and radioactively labeled vaccine components; (2) association and activation of immune cell subsets at the injection site, in the draining lymph node, and the spleen; (4) adaptive immune responses, such as cytotoxic T-lymphocytes, various T-helper cell subsets, and antibody responses, which may be quantitatively evaluated using ELISA, ELISPOT, and immunoplex assays and qualitatively evaluated using flow cytometric and single cell sequencing assays; and (5) effector responses, for example, antigen-specific cytotoxic potential of CD8+ T cells and antibody neutralization assays. While the vaccine-induced immune responses in mice often correlate with the responses induced in humans, there are instances where immune responses detected in mice are not translated to the human situation. We discuss some examples of correlation and discrepancy between mouse and human immune responses and how to understand them.


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