scholarly journals B1a B cells require autophagy for metabolic homeostasis and self-renewal

2017 ◽  
Author(s):  
Alexander J Clarke ◽  
Thomas Riffelmacher ◽  
Daniel Braas ◽  
Richard J Cornall ◽  
Anna Katharina Simon
Keyword(s):  
Fatty Acids ◽  
B Cells ◽  
Oxidative Phosphorylation ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Self Renewal ◽  
Functional Roles ◽  
Metabolic Genes ◽  
Autophagy Gene ◽  
B1 B Cells

AbstractSpecific metabolic programs are activated by immune cells to fulfil their functional roles, which include adaptations to their microenvironment. B1 B cells are tissue-resident, innate-like B cells. They have many distinct properties, such as the capacity to self-renew and the ability to rapidly respond to a limited repertoire of epitopes. The metabolic pathways that support these functions are unknown. We show that B1 B cells are bioenergetically more active than B2 B cells, with higher rates of glycolysis and oxidative phosphorylation, and depend on glycolysis. They acquire exogenous fatty acids, and store lipids in droplet form. Autophagy is differentially activated in B1a B cells, and deletion of the autophagy gene Atg7 leads to a selective loss of B1a B cells due to a failure of self-renewal. Autophagy-deficient B1a B cells downregulate critical metabolic genes and accumulate dysfunctional mitochondria. B1 B cells therefore, have evolved a distinct metabolism adapted to their residence and specific functional properties.

scholarly journals B1a B cells require autophagy for metabolic homeostasis and self-renewal

2018 ◽  
Vol 215 (2) ◽  
pp. 399-413 ◽  
Author(s):  
Alexander J. Clarke ◽  
Thomas Riffelmacher ◽  
Daniel Braas ◽  
Richard J. Cornall ◽  
Anna Katharina Simon
Keyword(s):  
Fatty Acids ◽  
B Cells ◽  
Oxidative Phosphorylation ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Self Renewal ◽  
Functional Roles ◽  
Metabolic Genes ◽  
Autophagy Gene ◽  
B1 B Cells

Specific metabolic programs are activated by immune cells to fulfill their functional roles, which include adaptations to their microenvironment. B1 B cells are tissue-resident, innate-like B cells. They have many distinct properties, such as the capacity to self-renew and the ability to rapidly respond to a limited repertoire of epitopes. The metabolic pathways that support these functions are unknown. We show that B1 B cells are bioenergetically more active than B2 B cells, with higher rates of glycolysis and oxidative phosphorylation, and depend on glycolysis. They acquire exogenous fatty acids and store lipids in droplet form. Autophagy is differentially activated in B1a B cells, and deletion of the autophagy gene Atg7 leads to a selective loss of B1a B cells caused by a failure of self-renewal. Autophagy-deficient B1a B cells down-regulate critical metabolic genes and accumulate dysfunctional mitochondria. B1 B cells, therefore, have evolved a distinct metabolism adapted to their residence and specific functional properties.

Metabolic Regulation and Related Molecular Mechanisms in Various Stem Cell Functions

2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Metabolic Pathways ◽  
Critical Role ◽  
The Self ◽  
Specific Cell ◽  
Differentiation Potential ◽  
Self Renewal ◽  
Cell Functions

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.

scholarly journals Associations of serum short-chain fatty acids with circulating immune cells and serum biomarkers in patients with multiple sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie Trend ◽  
Jonatan Leffler ◽  
Anderson P. Jones ◽  
Lilian Cha ◽  
Shelley Gorman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Fatty Acids ◽  
B Cells ◽  
Immune Cells ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Bioactive Metabolites ◽  
Healthy Controls ◽  
Serum Factors ◽  
Chain Fatty Acids

AbstractAltered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS). However, the immunomodulatory actions of SCFAs and intermediaries in their ability to influence MS pathogenesis are uncertain. In this study, levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood samples taken at first presentation of Clinically Isolated Syndrome (CIS; an early form of MS) or MS and compared to healthy controls. There was a small but significant reduction in propionate levels in the serum of patients with CIS or MS compared with healthy controls. The frequencies of circulating T follicular regulatory cells and T follicular helper cells were significantly positively correlated with serum levels of propionate. Levels of butyrate associated positively with frequencies of IL-10-producing B-cells and negatively with frequencies of class-switched memory B-cells. TNF production by polyclonally-activated B-cells correlated negatively with acetate levels. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS.

scholarly journals Tissue Metabolic Changes Drive Cytokine Responses to Mycobacterium tuberculosis

2018 ◽  
Vol 218 (1) ◽  
pp. 165-170 ◽  
Author(s):  
Ekta Lachmandas ◽  
Ana B Rios-Miguel ◽  
Valerie A C M Koeken ◽  
Eva van der Pasch ◽  
Vinod Kumar ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Cells ◽  
Human Tissue ◽  
Metabolic Pathways ◽  
Variable Expression ◽  
Metabolic Genes ◽  
Cytokine Responses ◽  
Expression Of Genes ◽  
Mycobacterial Antigens ◽  
Differential Expression Of Genes

Our study reveals that human tissue challenged with mycobacterial antigens induces differential expression of genes that regulate multiple metabolic pathways. We demonstrate that variable expression of these metabolic genes influences the cytokine response of immune cells stimulated by Mycobacterium tuberculosis.

Cancer stemness as a target for immunotherapy is shaped by pro-inflammatory stress.

2020 ◽  
Vol 15 ◽  
Author(s):  
Nese Unver
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Immune Cells ◽  
Tumor Recurrence ◽  
Inflammatory Factors ◽  
Cancer Stemness ◽  
Self Renewal ◽  
Inflammatory Stress ◽  
Factors Affecting

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.

scholarly journals The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 460
Author(s):  
Mohammed Hamed Alqarni ◽  
Ahmed Ibrahim Foudah ◽  
Magdy Mohamed Muharram ◽  
Nikolaos E. Labrou
Keyword(s):  
Metabolic Pathways ◽  
Histone Deacetylases ◽  
Viral Infections ◽  
Cell Physiology ◽  
Functional Roles ◽  
Regulatory Processes ◽  
Complex Functions ◽  
Natural Polyphenol ◽  
Antiviral Targets

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that incorporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained network of metabolic pathways that control and adapt the cell to the environment, energy availability and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promising antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection. In the present review, we summarize some of the recent progress in SIRTs biochemistry and their emerging function as antiviral targets. We also discuss the potential of natural polyphenol-based SIRT modulators to control their functional roles in several diseases including viral infections.

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 Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 240
Author(s):  
Alison Woodward ◽  
Alina Pandele ◽  
Salah Abdelrazig ◽  
Catherine A. Ortori ◽  
Iqbal Khan ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Extraction Method ◽  
Limit Of Detection ◽  
Rna Extraction ◽  
Extraction Process ◽  
Extraction Methods ◽  
Serum Starvation ◽  
Extraction Techniques ◽  
Metabolic Genes ◽  
Dual Extraction

The integration of untargeted metabolomics and transcriptomics from the same population of cells or tissue enhances the confidence in the identified metabolic pathways and understanding of the enzyme–metabolite relationship. Here, we optimised a simultaneous extraction method of metabolites/lipids and RNA from ependymoma cells (BXD-1425). Relative to established RNA (mirVana kit) or metabolite (sequential solvent addition and shaking) single extraction methods, four dual-extraction techniques were evaluated and compared (methanol:water:chloroform ratios): cryomill/mirVana (1:1:2); cryomill-wash/Econospin (5:1:2); rotation/phenol-chloroform (9:10:1); Sequential/mirVana (1:1:3). All methods extracted the same metabolites, yet rotation/phenol-chloroform did not extract lipids. Cryomill/mirVana and sequential/mirVana recovered the highest amounts of RNA, at 70 and 68% of that recovered with mirVana kit alone. sequential/mirVana, involving RNA extraction from the interphase of our established sequential solvent addition and shaking metabolomics-lipidomics extraction method, was the most efficient approach overall. Sequential/mirVana was applied to study a) the biological effect caused by acute serum starvation in BXD-1425 cells and b) primary ependymoma tumour tissue. We found (a) 64 differentially abundant metabolites and 28 differentially expressed metabolic genes, discovering four gene-metabolite interactions, and (b) all metabolites and 62% lipids were above the limit of detection, and RNA yield was sufficient for transcriptomics, in just 10 mg of tissue.

scholarly journals Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 453
Author(s):  
Camilla Kofoed Andersen ◽  
Sangita Khatri ◽  
Jonas Hansen ◽  
Sofie Slott ◽  
Rohith Pavan Parvathaneni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Carbon Nanotubes ◽  
B Cells ◽  
Human Blood ◽  
Immune Cells ◽  
Bone Marrow Cells ◽  
Coupling Efficiency ◽  
Drug Carriers ◽  
Whole Body ◽  
Whole Body Imaging

Two types of single-walled carbon nanotubes (SWCNTs), HiPco- and carboxyl-SWCNT, are evaluated as drug carriers for the traditional anti-inflammatory drug methotrexate (MTX) and a small interfering RNA (siRNA) targeting NOTCH1 gene. The nanotubes are solubilized by PEGylation and covalently loaded with MTX. The coupling efficiency (CE%) of MTX is 77–79% for HiPco-SWCNT and 71–83% for carboxyl-SWCNT. siRNA is noncovalently attached to the nanotubes with efficiency of 90–97% for HiPco-SWCNT and 87–98% for carboxyl-SWCNT. Through whole body imaging in the second near-infrared window (NIR-II window, 1000–1700 nm), SWCNTs were found to be selectively accumulated in inflamed joints in a serum transfer mouse model. We further investigated the interactions of the siRNA/MTX loaded nanotubes with human blood and mice bone marrow cells. In human blood, both types of unloaded SWCNTs were associated with B cells, monocytes and neutrophils. Interestingly, loading with MTX suppressed SWCNTs targeting specificity to immune cells, especially B cells; in contrast, loading siRNA alone enhanced the targeting specificity. Loading both MTX and siRNA to carboxyl-SWCNT enhanced targeting specificity to neutrophils and monocytes but not B cells. The targeting specificity of SWCNTs can potentially be adjusted by altering the ratio of MTX and siRNA loaded. The combined results show that carbon nanotubes have the potential for delivery of cargo drugs specifically to immune cells involved in rheumatoid arthritis.

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