How the redox state regulates immunity

Mullen, Lisa; Mengozzi, Manuela; Hanschmann, Eva-Maria; Alberts, Ben M.; Ghezzi, Pietro

doi:10.1016/j.freeradbiomed.2019.12.022

Cited by 54 publications

(45 citation statements)

References 180 publications

(203 reference statements)

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“…The system is highly flexible and tunable, providing redox modulation that is dependent on actual needs. The other way around, glucose flows and redox state regulate the function of immune system[121]. Failure of feedback loops and distorted signaling-either from CNS (stress), the immune system (inflammation) or the malfunction of peripheral sensors-lead to excessive, uncontrolled (poorly controlled) glucose release and/or the activation of gluconeogenesis, leading to diabetes.…”

mentioning

confidence: 99%

Glucose as a Major Antioxidant: When, What for and Why It Fails?

et al. 2020

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A human organism depends on stable glucose blood levels in order to maintain its metabolic needs. Glucose is considered to be the most important energy source, and glycolysis is postulated as a backbone pathway. However, when the glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of the pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. The PPP generates and maintains the levels of nicotinamide adenine dinucleotide phosphate (NADPH) needed for the reduction in oxidized glutathione and protein thiols, the synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. The flux of glucose into a PPP—particularly under extreme oxidative and toxic challenges—is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP+ that is required for the activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain the disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload, and provide new insights into the positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.

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mentioning

confidence: 99%

Glucose as a Major Antioxidant: When, What for and Why It Fails?

et al. 2020

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“…Multiple evidence showed that ROS are involved in sensing danger, that is, the presence of pathogens as well as tissue damage. Indeed, Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs) recognition by immune cells can trigger intracellular signaling events leading to increased ROS generation that can result in inflammasome activation and pro-inflammatory cytokine production [ 3 , 4 ]. ROS play also a critical regulatory role in determining the initiation and outcome of phagocytosis.…”

Section: Reactive Oxygen Species Role In Immunitymentioning

confidence: 99%

“…Indeed, ROS production is recognized as necessary for all stages of the inflammatory process. Both innate and adaptive immunity entail redox-regulated processes, for instance, the governance of immune cells infiltration, their activation and differentiation, the oxidative burst of phagocytes, as well as the control of cellular signal transduction and transcription programs [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species and Antitumor Immunity—From Surveillance to Evasion

Kotsafti

Scarpa

Castagliuolo

et al. 2020

Cancers

100

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The immune system is a crucial regulator of tumor biology with the capacity to support or inhibit cancer development, growth, invasion and metastasis. Emerging evidence show that reactive oxygen species (ROS) are not only mediators of oxidative stress but also players of immune regulation in tumor development. This review intends to discuss the mechanism by which ROS can affect the anti-tumor immune response, with particular emphasis on their role on cancer antigenicity, immunogenicity and shaping of the tumor immune microenvironment. Given the complex role that ROS play in the dynamics of cancer-immune cell interaction, further investigation is needed for the development of effective strategies combining ROS manipulation and immunotherapies for cancer treatment.

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“…The regulatory effect of oxidants on immunity was first evidenced when hydrogen peroxide at micromolar concentrations was able to activate the transcription factor nuclear factor-κB (NF-κB), a key determinant of the immune response; this effect was largely missing after a co-treatment with the antioxidant N-acetylcysteine (Schreck et al, 1991). Since then, several investigations addressed the immune-regulatory properties of oxidants in mild concentration, but also of oxidoreductant enzymes (Mullen et al, 2019).…”

Section: Cholestasismentioning

confidence: 99%

Redox Control of the Immune Response in the Hepatic Progenitor Cell Niche

Bellanti

Pannone

Tartaglia

et al. 2020

Front. Cell Dev. Biol.

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The liver commonly self-regenerates by a proliferation of mature cell types. Nevertheless, in case of severe or protracted damage, the organ renewal is mediated by the hepatic progenitor cells (HPCs), adult progenitors capable of differentiating toward the biliary and the hepatocyte lineages. This regeneration process is determined by the formation of a stereotypical niche surrounding the emerging progenitors. The organization of the HPC niche microenvironment is crucial to drive biliary or hepatocyte regeneration. Furthermore, this is the site of a complex immunological activity mediated by several immune and non-immune cells. Indeed, several cytokines produced by monocytes, macrophages and T-lymphocytes may promote the activation of HPCs in the niche. On the other side, HPCs may produce pro-inflammatory cytokines induced by liver inflammation. The inflamed liver is characterized by high generation of reactive oxygen and nitrogen species, which in turn lead to the oxidation of macromolecules and the alteration of signaling pathways. Reactive species and redox signaling are involved in both the immunological and the adult stem cell regeneration processes. It is then conceivable that redox balance may finely regulate the immune response in the HPC niche, modulating the regeneration process and the immune activity of HPCs. In this perspective article, we summarize the current knowledge on the role of reactive species in the regulation of hepatic immunity, suggesting future research directions for the study of redox signaling on the immunomodulatory properties of HPCs.

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How the redox state regulates immunity

Cited by 54 publications

References 180 publications

Glucose as a Major Antioxidant: When, What for and Why It Fails?

Glucose as a Major Antioxidant: When, What for and Why It Fails?

Reactive Oxygen Species and Antitumor Immunity—From Surveillance to Evasion

Redox Control of the Immune Response in the Hepatic Progenitor Cell Niche

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