The role of metabolic checkpoint regulators in B cell survival and transformation

Jellusova, Julia

doi:10.1111/imr.12855

Cited by 28 publications

(19 citation statements)

References 106 publications

(290 reference statements)

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“…Germinal centers also provide a dynamic microenvironment which may be hypoxic to drive glycolysis and alter B cell proliferation and fate, 31 although increased fatty acid metabolism in germinal center localized B cells has also been reported 46 . How these changes relate to the particular activation and differentiation states of B cells as they transition through activation, germinal centers, and plasmablast differentiation is discussed in detail by Jellusova 47 . Because germinal center B cells undergo class switch DNA recombination and somatic hypermutation, errors leading to mutations can occur.…”

Section: Basic Mechanisms That Regulate Immune Metabolismmentioning

confidence: 99%

Immunometabolism: From basic mechanisms to translation

Makowski

Chaib

Rathmell

2020

Immunological Reviews

218

141

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Immunometabolism has emerged as a major mechanism central to adaptive and innate immune regulation. From early observations that inflammatory cytokines were induced in obese adipose tissue and that these cytokines contributed to metabolic disease, it was clear that metabolism and the immunological state are inextricably linked. With a second research wave arising from studies in cancer metabolism to also study the intrinsic metabolic pathways of immune cells themselves and how those pathways influence cell fate and function, immunometabolism is a rapidly maturing area of research. Several key themes and goals drive the field. There is abundant evidence that metabolic pathways are closely tied to cell signaling and differentiation which leads different subsets of immune cells to adopt unique metabolic programs specific to their state and environment. In this way, metabolic signaling drives cell fate. It is also apparent that microenvironment greatly influences cell metabolism.Immune cells adopt programs specific for the tissues where they infiltrate and reside.Ultimately, a central goal of the field is to apply immunometabolism findings to the discovery of novel therapeutic strategies in a wide range of diseases, including cancer, autoimmunity, and metabolic syndrome. This review summarizes these facets of immunometabolism and highlights opportunities for clinical translation. K E Y W O R D S autoimmunity, immune-mediated diseases, infectious diseases, metThis article introduces a series of reviews covering Immunometabolism: From Basic Mechanisms to Translation appearing in Volume 295 of Immunological Reviews.

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Section: Basic Mechanisms That Regulate Immune Metabolismmentioning

confidence: 99%

Immunometabolism: From basic mechanisms to translation

Makowski

Chaib

Rathmell

2020

Immunological Reviews

218

141

View full text Add to dashboard Cite

show abstract

“…Increases in lactate and pyruvate can be interpreted as increased glycolysis in patients with high CRP, perhaps driven by hypoxia of carbon flow from pyruvate to acetyl-CoA. Increased glycolysis is a metabolic consequence of both immune cell activation and hypoxemia (Frauwirth et al, 2002; Jellusova, 2020; Makowski et al, 2020; Michalek et al, 2011; van Teijlingen Bakker and Pearce, 2020). Importantly, each of these three classes of metabolites represent entry points to the TCA cycle and elevated levels of these features are consistent with mitochondrial dysfunction and decreased activity in the TCA cycle and the electron transport chain (ETC).…”

Section: Resultsmentioning

confidence: 99%

The COVIDome Explorer Researcher Portal

Sullivan

Galbraith

Kinning

et al. 2021

Preprint

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COVID-19 pathology involves dysregulation of diverse molecular, cellular, and physiological processes. In order to expedite integrated and collaborative COVID-19 research, we completed multi-omics analysis of hospitalized COVID-19 patients including matched analysis of the whole blood transcriptome, plasma proteomics with two complementary platforms, cytokine profiling, plasma and red blood cell metabolomics, deep immune cell phenotyping by mass cytometry, and clinical data annotation. We refer to this multidimensional dataset as the COVIDome. We then created the COVIDome Explorer, an online researcher portal where the data can be analyzed and visualized in real time. We illustrate here the use of the COVIDome dataset through a multi-omics analysis of biosignatures associated with C-reactive protein (CRP), an established marker of poor prognosis in COVID-19, revealing associations between CRP levels and damage-associated molecular patterns, depletion of protective serpins, and mitochondrial metabolism dysregulation. We expect that the COVIDome Explorer will rapidly accelerate data sharing, hypothesis testing, and discoveries worldwide.

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“…For example, the OXPHOS pathway is important for Th17 differentiation, and the absence of OXPHOS during differentiation leads to regulatory T cell (Treg) development ( 79 , 80 ). B cells are rather unique in their metabolic program compared to other immune cells, relying heavily on FAO and minimally on glycolysis ( 81 , 82 ). There are few reports on the role of B cells during CNS infections, but available evidence shows important contributions for pathogen neutralization by enhanced opsonophagocytosis and complement activation ( 83 ).…”

Section: Pathogenic and Immune Characteristics Of Cns Infectionsmentioning

confidence: 99%

The Prospect of Nanoparticle Systems for Modulating Immune Cell Polarization During Central Nervous System Infection

et al. 2021

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The blood-brain barrier (BBB) selectively restricts the entry of molecules from peripheral circulation into the central nervous system (CNS) parenchyma. Despite this protective barrier, bacteria and other pathogens can still invade the CNS, often as a consequence of immune deficiencies or complications following neurosurgical procedures. These infections are difficult to treat since many bacteria, such as Staphylococcus aureus, encode a repertoire of virulence factors, can acquire antibiotic resistance, and form biofilm. Additionally, pathogens can leverage virulence factor production to polarize host immune cells towards an anti-inflammatory phenotype, leading to chronic infection. The difficulty of pathogen clearance is magnified by the fact that antibiotics and other treatments cannot easily penetrate the BBB, which requires extended regimens to achieve therapeutic concentrations. Nanoparticle systems are rapidly emerging as a promising platform to treat a range of CNS disorders. Nanoparticles have several advantages, as they can be engineered to cross the BBB with specific functionality to increase cellular and molecular targeting, have controlled release of therapeutic agents, and superior bioavailability and circulation compared to traditional therapies. Within the CNS environment, therapeutic actions are not limited to directly targeting the pathogen, but can also be tailored to modulate immune cell activation to promote infection resolution. This perspective highlights the factors leading to infection persistence in the CNS and discusses how novel nanoparticle therapies can be engineered to provide enhanced treatment, specifically through modulation of immune cell polarization.

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The role of metabolic checkpoint regulators in B cell survival and transformation

Cited by 28 publications

References 106 publications

Immunometabolism: From basic mechanisms to translation

Immunometabolism: From basic mechanisms to translation

The COVIDome Explorer Researcher Portal

The Prospect of Nanoparticle Systems for Modulating Immune Cell Polarization During Central Nervous System Infection

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