scholarly journals Regulation of Immune Cell Functions by Metabolic Reprogramming

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jaehong Kim
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Aerobic Glycolysis ◽  
Metabolic Changes ◽  
Metabolic Reprogramming ◽  
Functional Plasticity ◽  
Inflammatory Reactions ◽  
Cell Functions

Recent findings show that the metabolic status of immune cells can determine immune responses. Metabolic reprogramming between aerobic glycolysis and oxidative phosphorylation, previously speculated as exclusively observable in cancer cells, exists in various types of immune and stromal cells in many different pathological conditions other than cancer. The microenvironments of cancer, obese adipose, and wound-repairing tissues share common features of inflammatory reactions. In addition, the metabolic changes in macrophages and T cells are now regarded as crucial for the functional plasticity of the immune cells and responsible for the progression and regression of many pathological processes, notably cancer. It is possible that metabolic changes in the microenvironment induced by other cellular components are responsible for the functional plasticity of immune cells. This review explores the molecular mechanisms responsible for metabolic reprogramming in macrophages and T cells and also provides a summary of recent updates with regard to the functional modulation of the immune cells by metabolic changes in the microenvironment, notably the tumor microenvironment.

scholarly journals Dietary Intervention Impacts Immune Cell Functions and Dynamics by Inducing Metabolic Rewiring

2021 ◽  
Vol 11 ◽  
Author(s):  
Takuma Okawa ◽  
Motoyoshi Nagai ◽  
Koji Hase
Keyword(s):  
T Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Dietary Intervention ◽  
Immune Cell ◽  
Aerobic Glycolysis ◽  
Acid Oxidation ◽  
Intermittent Fasting ◽  
Cell Trafficking ◽  
Cell Functions

Accumulating evidence has shown that nutrient metabolism is closely associated with the differentiation and functions of various immune cells. Cellular metabolism, including aerobic glycolysis, fatty acid oxidation, and oxidative phosphorylation, plays a key role in germinal center (GC) reaction, B-cell trafficking, and T-cell-fate decision. Furthermore, a quiescent metabolic status consolidates T-cell-dependent immunological memory. Therefore, dietary interventions such as calorie restriction, time-restricted feeding, and fasting potentially manipulate immune cell functions. For instance, intermittent fasting prevents the development of experimental autoimmune encephalomyelitis. Meanwhile, the fasting response diminishes the lymphocyte pool in gut-associated lymphoid tissue to minimize energy expenditure, leading to the attenuation of Immunoglobulin A (IgA) response. The nutritional status also influences the dynamics of several immune cell subsets. Here, we describe the current understanding of the significance of immunometabolism in the differentiation and functionality of lymphocytes and macrophages. The underlying molecular mechanisms also are discussed. These experimental observations could offer new therapeutic strategies for immunological disorders like autoimmunity.

scholarly journals Regulation of Immune Functions by Non-Neuronal Acetylcholine (ACh) via Muscarinic and Nicotinic ACh Receptors

2021 ◽  
Vol 22 (13) ◽  
pp. 6818
Author(s):  
Masato Mashimo ◽  
Yasuhiro Moriwaki ◽  
Hidemi Misawa ◽  
Koichiro Kawashima ◽  
Takeshi Fujii
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Functions ◽  
Cell Functions ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Cellular And Humoral Immunity ◽  
Ach Receptors

Acetylcholine (ACh) is the classical neurotransmitter in the cholinergic nervous system. However, ACh is now known to regulate various immune cell functions. In fact, T cells, B cells, and macrophages all express components of the cholinergic system, including ACh, muscarinic, and nicotinic ACh receptors (mAChRs and nAChRs), choline acetyltransferase, acetylcholinesterase, and choline transporters. In this review, we will discuss the actions of ACh in the immune system. We will first briefly describe the mechanisms by which ACh is stored in and released from immune cells. We will then address Ca2+ signaling pathways activated via mAChRs and nAChRs on T cells and B cells, highlighting the importance of ACh for the function of T cells, B cells, and macrophages, as well as its impact on innate and acquired (cellular and humoral) immunity. Lastly, we will discuss the effects of two peptide ligands, secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide-1 (SLURP-1) and hippocampal cholinergic neurostimulating peptide (HCNP), on cholinergic activity in T cells. Overall, we stress the fact that ACh does not function only as a neurotransmitter; it impacts immunity by exerting diverse effects on immune cells via mAChRs and nAChRs.

scholarly journals Molecular profiles and immunomodulatory activities of glioblastoma-derived exosomes

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Juliana Hofstatter Azambuja ◽  
Nils Ludwig ◽  
Saigopalakrishna Yerneni ◽  
Aparna Rao ◽  
Elizandra Braganhol ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Size Exclusion ◽  
Cell Functions

Abstract Background Glioblastoma is one of the most immunosuppressive human tumors. Emerging data suggest that glioblastoma-derived exosomes (GBex) reprogram the tumor microenvironment into a tumor-promoting milieu by mechanisms that not yet understood. Methods Exosomes were isolated from supernatants of glioblastoma cell lines by size exclusion chromatography. The GBex endosomal origin, size, protein cargos, and ex vivo effects on immune cell functions were determined. GBex were injected intravenously into mice to evaluate their ability to in vivo modulate normal immune cell subsets. Results GBex carried immunosuppressive proteins, including FasL, TRAIL, CTLA-4, CD39, and CD73, but contained few immunostimulatory proteins. GBex co-incubated with primary human immune cells induced simultaneous activation of multiple molecular pathways. In CD8+ T cells, GBex suppressed TNF-α and INF-γ release and mediated apoptosis. GBex suppressed natural killer (NK) and CD4+ T-cell activation. GBex activated the NF-κB pathway in macrophages and promoted their differentiation into M2 cells. Inhibition of the NF-κB pathway in macrophages reversed the GBex-mediated effects. GBex-driven reprogramming of macrophages involved the release of soluble factors that promoted tumor proliferation in vitro. In mice injected with GBex, the frequency of splenic CD8+ T cells, NK cells, and M1-like macrophages was reduced, while that of naïve and M2-like macrophages increased (P < .05). Conclusions GBex reprogrammed functions of all types of immune cells in vitro and altered their frequency in vivo. By creating and sustaining a highly immunosuppressive environment, GBex play a key role in promoting tumor progression.

scholarly journals Amino acids: key sources for immunometabolites and immunotransmitters

2020 ◽  
Vol 32 (7) ◽  
pp. 435-446 ◽  
Author(s):  
Michio Miyajima
Keyword(s):  
Amino Acids ◽  
Immune Cells ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cell Activation ◽  
Immune Cell ◽  
Nerve Cells ◽  
Metabolic Reprogramming ◽  
Functional Plasticity ◽  
Immune Cell Activation ◽  
Oxide Synthase

Abstract Immune-cell activation and functional plasticity are closely linked to metabolic reprogramming that is required to supply the energy and substrates for such dynamic transformations. During such processes, immune cells metabolize many kinds of molecules including nucleic acids, sugars and lipids, which is called immunometabolism. This review will mainly focus on amino acids and their derivatives among such metabolites and describe the functions of these molecules in the immune system. Although amino acids are essential for, and well known as, substrates for protein synthesis, they are also metabolized as energy sources and as substrates for functional catabolites. For example, glutamine is metabolized to produce energy through glutaminolysis and tryptophan is consumed to supply nicotinamide adenine dinucleotide, whereas arginine is metabolized to produce nitric acid and polyamine by nitric oxide synthase and arginase, respectively. In addition, serine is catabolized to produce nucleotides and to induce methylation reactions. Furthermore, in addition to their intracellular functions, amino acids and their derivatives are secreted and have extracellular functions as immunotransmitters. Many amino acids and their derivatives have been classified as neurotransmitters and their functions are clear as transmitters between nerve cells, or between nerve cells and immune cells, functioning as immunotransmitters. Thus, this review will describe the intracellular and external functions of amino acid from the perspective of immunometabolism and immunotransmission.

scholarly journals Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 125 ◽  
Author(s):  
Clovis S. Palmer ◽  
Riya Palchaudhuri ◽  
Hassan Albargy ◽  
Mohamed Abdel-Mohsen ◽  
Suzanne M. Crowe
Keyword(s):  
Hiv Infection ◽  
Immune Cells ◽  
Cell Activation ◽  
Viral Infections ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Low Grade ◽  
Hiv Cure ◽  
Cell Functions ◽  
Age Related

An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated. A clearer insight into how these processes are inter-related will affect our understanding of several fundamental aspects of HIV persistence. Even in patients with long-term use of anti-retroviral therapies, HIV infection persists and continues to cause chronic immune activation and inflammation, ongoing and cumulative damage to multiple organs systems, and a reduction in life expectancy. HIV-associated fundamental changes to the metabolic machinery of the immune system can promote a state of “inflammaging”, a chronic, low-grade inflammation with specific immune changes that characterize aging, and can also contribute to the persistence of HIV in its reservoirs. In this commentary, we will bring into focus evolving concepts on how HIV modulates the metabolic machinery of immune cells in order to persist in reservoirs and how metabolic reprogramming facilitates a chronic state of inflammation that underlies the development of age-related comorbidities. We will discuss how immunometabolism is facilitating the changing paradigms in HIV cure research and outline the novel therapeutic opportunities for preventing inflammaging and premature development of age-related conditions in HIV+individuals.

scholarly journals Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2423
Author(s):  
Jacopo Albanesi ◽  
Nelida Ines Noguera ◽  
Cristina Banella ◽  
Tommaso Colangelo ◽  
Elisabetta De Marinis ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Aerobic Glycolysis ◽  
Therapy Resistance ◽  
Therapeutic Strategies ◽  
Promyelocytic Leukemia ◽  
Metabolic Reprogramming ◽  
Granulocytic Differentiation ◽  
Nb4 Cells

Acute promyelocytic leukemia (APL) is a hematological disease characterized by a balanced reciprocal translocation that leads to the synthesis of the oncogenic fusion protein PML-RARα. APL is mainly managed by a differentiation therapy based on the administration of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, therapy resistance, differentiation syndrome, and relapses require the development of new low-toxicity therapies based on the induction of blasts differentiation. In keeping with this, we reasoned that a better understanding of the molecular mechanisms pivotal for ATRA-driven differentiation could definitely bolster the identification of new therapeutic strategies in APL patients. We thus performed an in-depth high-throughput transcriptional profile analysis and metabolic characterization of a well-established APL experimental model based on NB4 cells that represent an unevaluable tool to dissect the complex mechanism associated with ATRA-induced granulocytic differentiation. Pathway-reconstruction analysis using genome-wide transcriptional data has allowed us to identify the activation/inhibition of several cancer signaling pathways (e.g., inflammation, immune cell response, DNA repair, and cell proliferation) and master regulators (e.g., transcription factors, epigenetic regulators, and ligand-dependent nuclear receptors). Furthermore, we provide evidence of the regulation of a considerable set of metabolic genes involved in cancer metabolic reprogramming. Consistently, we found that ATRA treatment of NB4 cells drives the activation of aerobic glycolysis pathway and the reduction of OXPHOS-dependent ATP production. Overall, this study represents an important resource in understanding the molecular “portfolio” pivotal for APL differentiation, which can be explored for developing new therapeutic strategies.

scholarly journals IFN-γPriming Effects on the Maintenance of Effector Memory CD4+T Cells and on Phagocyte Function: Evidences from Infectious Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Henrique Borges da Silva ◽  
Raíssa Fonseca ◽  
José M. Alvarez ◽  
Maria Regina D’Império Lima
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Effector Memory ◽  
Innate Immune Cells ◽  
Chronic Infections ◽  
Cell Functions ◽  
Memory Cd4 T Cells

Although it has been established that effector memory CD4+T cells play an important role in the protective immunity against chronic infections, little is known about the exact mechanisms responsible for their functioning and maintenance, as well as their effects on innate immune cells. Here we review recent data on the role of IFN-γpriming as a mechanism affecting both innate immune cells and effector memory CD4+T cells. Suboptimal concentrations of IFN-γare seemingly crucial for the optimization of innate immune cell functions (including phagocytosis and destruction of reminiscent pathogens), as well as for the survival and functioning of effector memory CD4+T cells. Thus, IFN-γpriming can thus be considered an important bridge between innate and adaptive immunity.

scholarly journals Complement Has Brains—Do Intracellular Complement and Immunometabolism Cooperate in Tissue Homeostasis and Behavior?

2021 ◽  
Vol 12 ◽  
Author(s):  
Natalia Kunz ◽  
Claudia Kemper
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Complement System ◽  
Immune Cell ◽  
Cell Activity ◽  
Metabolic Reprogramming ◽  
Normal Brain ◽  
Peripheral Tissues ◽  
Ifn Γ ◽  
The Brain

The classical liver-derived and serum-effective complement system is well appreciated as a key mediator of host protection via instruction of innate and adaptive immunity. However, recent studies have discovered an intracellularly active complement system, the complosome, which has emerged as a central regulator of the core metabolic pathways fueling human immune cell activity. Induction of expression of components of the complosome, particularly complement component C3, during transmigration from the circulation into peripheral tissues is a defining characteristic of monocytes and T cells in tissues. Intracellular complement activity is required to induce metabolic reprogramming of immune cells, including increased glycolytic flux and OXPHOS, which drive the production of the pro-inflammatory cytokine IFN-γ. Consequently, reduced complosome activity translates into defects in normal monocyte activation, faulty Th1 and cytotoxic T lymphocyte responses and loss of protective tissue immunity. Intriguingly, neurological research has identified an unexpected connection between the physiological presence of innate and adaptive immune cells and certain cytokines, including IFN-γ, in and around the brain and normal brain function. In this opinion piece, we will first review the current state of research regarding complement driven metabolic reprogramming in the context of immune cell tissue entry and residency. We will then discuss how published work on the role of IFN-γ and T cells in the brain support a hypothesis that an evolutionarily conserved cooperation between the complosome, cell metabolism and IFN-γ regulates organismal behavior, as well as immunity.

scholarly journals Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

2020 ◽  
Author(s):  
Naiqiang Zhu ◽  
Jingyi Hou
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Blue Module

Abstract Background: Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas.Method: The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization. Results: Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level.Conclusion: Based on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis.

scholarly journals Assessing immune infiltration and the tumor microenvironment for the diagnosis and prognosis of sarcoma

2020 ◽  
Author(s):  
Naiqiang Zhu ◽  
Jingyi Hou
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Blue Module

Abstract Background: Sarcomas, cancers originating from mesenchymal cells, are comprehensive tumors with poor prognoses, yet their tumorigenic mechanisms are largely unknown. In this study, we characterize infiltrating immune cells and analyze immune scores to identify the molecular mechanism of immunologic response to sarcomas.Method: The “CIBERSORT” algorithm was used to calculate the amount of L22 immune cell infiltration in sarcomas. Then, the “ESTIMATE” algorithm was used to assess the “Estimate,” “Immune,” and “Stromal” scores. Weighted gene co-expression network analysis (WGCNA) was utilized to identify the significant module related to the immune therapeutic target. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the “clusterProfiler” package in R for annotation and visualization. Results: Macrophages were the most common immune cells infiltrating sarcomas. The number of CD8 T cells was negatively associated with that of M0 and M2 macrophages, and positively associated with M macrophages in sarcomas samples. The clinical parameters (disease type, gender) significantly increased with higher Estimate, Immune, and Stromal scores, and with a better prognosis. The blue module was significantly associated with CD8 T cells. Functional enrichment analysis showed that the blue module was mainly involved in chemokine signaling and the PI3K-Akt signaling pathway. CD48, P2RY10 and RASAL3 were identified and validated at the protein level.Conclusion: Based on the immune cell infiltration and immune microenvironment, three key genes were identified, thus presenting novel molecular mechanisms of sarcoma metastasis.

Sign in / Sign up

Export Citation Format

Share Document