Redox regulation of immunometabolism

Muri, Jonathan; Köpf, Manfred

doi:10.1038/s41577-020-00478-8

Cited by 313 publications

(234 citation statements)

References 275 publications

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“…The immune system is continuously influenced by hormetic effects of environmental compounds (e.g., chemicals), physical influences (background irradiations, major change of temperature), or medical (drugs) and food interactions [44]. Low-level ROS activates the main cellular antioxidant pathways (e.g., thioredoxin (TRX) and GSH) as well as their transcriptional regulator Nrf2 [45].…”

Section: Other Hormetic Effects In the Immune Systemmentioning

confidence: 99%

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Schirrmacher¹

2021

Biomedicines

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A dose-response relationship to stressors, according to the hormesis theory, is characterized by low-dose stimulation and high-dose inhibition. It is non-linear with a low-dose optimum. Stress responses by cells lead to adapted vitality and fitness. Physical stress can be exerted through heat, radiation, or physical exercise. Chemical stressors include reactive species from oxygen (ROS), nitrogen (RNS), and carbon (RCS), carcinogens, elements, such as lithium (Li) and silicon (Si), and metals, such as silver (Ag), cadmium (Cd), and lead (Pb). Anthropogenic chemicals are agrochemicals (phytotoxins, herbicides), industrial chemicals, and pharmaceuticals. Biochemical stress can be exerted through toxins, medical drugs (e.g., cytostatics, psychopharmaceuticals, non-steroidal inhibitors of inflammation), and through fasting (dietary restriction). Key-lock interactions between enzymes and substrates, antigens and antibodies, antigen-presenting cells, and cognate T cells are the basics of biology, biochemistry, and immunology. Their rules do not obey linear dose-response relationships. The review provides examples of biologic stressors: oncolytic viruses (e.g., immuno-virotherapy of cancer) and hormones (e.g., melatonin, stress hormones). Molecular mechanisms of cellular stress adaptation involve the protein quality control system (PQS) and homeostasis of proteasome, endoplasmic reticulum, and mitochondria. Important components are transcription factors (e.g., Nrf2), micro-RNAs, heat shock proteins, ionic calcium, and enzymes (e.g., glutathion redox enzymes, DNA methyltransferases, and DNA repair enzymes). Cellular growth control, intercellular communication, and resistance to stress from microbial infections involve growth factors, cytokines, chemokines, interferons, and their respective receptors. The effects of hormesis during evolution are multifarious: cell protection and survival, evolutionary flexibility, and epigenetic memory. According to the hormesis theory, this is true for the entire biosphere, e.g., archaia, bacteria, fungi, plants, and the animal kingdoms.

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Section: Other Hormetic Effects In the Immune Systemmentioning

confidence: 99%

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Schirrmacher¹

2021

Biomedicines

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“…Accumulation of glycolytic intermediates and byproducts further support primary functions of activated macrophages, including providing glucose-6-phosphate to the pentose phosphate pathway (PPP) which contributes to both building of biomass and regulating the redox state, as well as induce the production of immune effectors such as itaconate and IL-1b [summarized in depth here (69)]. Building from this work, numerous studies have demonstrated the importance of this metabolic switch for key inflammatory macrophage functions, including bacterial phagocytosis, production of pro-inflammatory cytokines, synthesis of antimicrobial peptides, and generation of reactive oxygen species (ROS) (76)(77)(78)(79). Collectively, this work demonstrates that quiescent macrophages undergo striking metabolic changes in support of one of its core immunological roles as a defender against invading pathogens (Figure 1).…”

Section: Pro-inflammatory Macrophagesmentioning

confidence: 99%

“…In mouse macrophages, it is generally thought that arginine is catabolized via two distinct routes: via an inducible nitric oxide synthase (iNOS) catalyzed dehydration reaction that produces citrulline and nitric oxide or by an arginase 1 (Arg1) catalyzed hydrolysis reaction that produces ornithine and urea (77). The former reaction is thought to be a key component of the pro-inflammatory macrophage response to pathogen invasion (78), whereas the latter is thought to be a key step to the generation of pro-resolving macrophages (81). Ornithine, and its conversion to putrescine via ornithine decarboxylase (ODC), as part of polyamine synthesis, is essential for multiple facets of the induction and maintenance of pro-resolving macrophages (89) (Figure 2).…”

Section: Pro-resolving Macrophagesmentioning

confidence: 99%

Immunometabolism of Tissue-Resident Macrophages – An Appraisal of the Current Knowledge and Cutting-Edge Methods and Technologies

et al. 2021

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Tissue-resident macrophages exist in unique environments, or niches, that inform their identity and function. There is an emerging body of literature suggesting that the qualities of this environment, such as the types of cells and debris they eat, the intercellular interactions they form, and the length of time spent in residence, collectively what we call habitare, directly inform their metabolic state. In turn, a tissue-resident macrophage’s metabolic state can inform their function, including whether they resolve inflammation and protect the host from excessive perturbations of homeostasis. In this review, we summarize recent work that seeks to understand the metabolic requirements for tissue-resident macrophage identity and maintenance, for how they respond to inflammatory challenges, and for how they perform homeostatic functions or resolve inflammatory insults. We end with a discussion of the emerging technologies that are enabling, or will enable, in situ study of tissue-resident macrophage metabolism.

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“…GSS involved in the synthesis of glutathione (GSH), an important antioxidant in mammalian cells (37). Because the increased level of ROS contributed to the inability of MDSCs differentiation (38), we intended to explore whether acitretin promoted the differentiation of MDSCs by regulating glutathione metabolism.…”

Section: Mechanism Of Acitretin Effect On the Differentiation Of Mdscsmentioning

confidence: 99%

Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis

Peng

Chen

et al. 2021

Front. Med.

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Increased numbers of myeloid-derived suppressor cells (MDSCs) are involved in the development of psoriasis. Acitretin is used to treat psoriasis by regulating the proliferation and differentiation of keratinocytes, but little is known about the effect of acitretin on immune cells. Here, we reported that psoriasis patients had an expansion of MDSCs and monocytic-MDSCs (M-MDSCs) in peripheral blood and skin lesions. The number of MDSCs and M-MDSCs in peripheral blood correlated positively with disease severity. Acitretin could reduce the number of MDSCs and M-MDSCs in the peripheral blood of psoriasis patients as well as the spleen and skin lesions of IMQ-induced psoriasis-like model mice. Moreover, acitretin promoted the differentiation of MDSCs into macrophages, especially CD206+ M2 macrophages, and CD11c+MHC-II+ dendritic cells. Mechanically, acitretin dramatically increased the glutathione synthase (GSS) expression and glutathione (GSH) accumulation in MDSCs. Interruption of GSH synthesis abrogated the acitretin effect on MDSCs differentiation. Acitretin regulated GSS expression via activation of extracellular signal-regulated kinase 1/2. Thus, our data demonstrated a novel mechanism underlying the effects of acitretin on psoriasis by promoting MDSCs differentiation.

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Redox regulation of immunometabolism

Cited by 313 publications

References 275 publications

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Less Can Be More: The Hormesis Theory of Stress Adaptation in the Global Biosphere and Its Implications

Immunometabolism of Tissue-Resident Macrophages – An Appraisal of the Current Knowledge and Cutting-Edge Methods and Technologies

Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis

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