Two Faces of Macrophages: Training and Tolerance

Zubair, Kiran; You, Chaelin; Kwon, Geunho; Kang, Ki‐Woon

doi:10.3390/biomedicines9111596

Cited by 26 publications

(27 citation statements)

References 161 publications

(219 reference statements)

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“…On the one hand, innate immune cells, including macrophages, are already well trained for certain stimuli to respond more strongly and activate the immune system to keep our body safe. On the other hand, the immune tolerance characteristics of macrophages help maintain immune balance [ 93 ]. In autoimmune diseases, macrophages, in the same way as trucks that have lost their brakes, continuously respond to proinflammatory factors in the microenvironment and amplify these signals.…”

Section: Macrophages In Autoimmune Disease Kidney Damage and Repairmentioning

confidence: 99%

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Tian

Chen

Zhang

et al. 2022

IJMS

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Chronic kidney disease (CKD), as one of the main complications of many autoimmune diseases, is difficult to cure, which places a huge burden on patients’ health and the economy and poses a great threat to human health. At present, the mainstream view is that autoimmune diseases are a series of diseases and complications caused by immune cell dysfunction leading to the attack of an organism’s tissues by its immune cells. The kidney is the organ most seriously affected by autoimmune diseases as it has a very close relationship with immune cells. With the development of an in-depth understanding of cell metabolism in recent years, an increasing number of scientists have discovered the metabolic changes in immune cells in the process of disease development, and we have a clearer understanding of the characteristics of the metabolic changes in immune cells. This suggests that the regulation of immune cell metabolism provides a new direction for the treatment and prevention of kidney damage caused by autoimmune diseases. Macrophages are important immune cells and are a double-edged sword in the repair process of kidney injury. Although they can repair damaged kidney tissue, over-repair will also lead to the loss of renal structural reconstruction function. In this review, from the perspective of metabolism, the metabolic characteristics of macrophages in the process of renal injury induced by autoimmune diseases are described, and the metabolites that can regulate the function of macrophages are summarized. We believe that treating macrophage metabolism as a target can provide new ideas for the treatment of the renal injury caused by autoimmune diseases.

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Section: Macrophages In Autoimmune Disease Kidney Damage and Repairmentioning

confidence: 99%

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Tian

Chen

Zhang

et al. 2022

IJMS

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“…An increasing amount of evidence pointed out that histone acetylation plays an important role in the modulation in monocytes and macrophages ( Das Gupta et al, 2016 ). In particular, H3 acetylation plays an important role in macrophage phenotypic gene expression ( Figure 2 ) ( Zubair et al, 2021 ). Among the HDACs, HDAC3 acts as a key modulator in M1 macrophage polarization, thereby blocking M2 macrophage polarization ( Figure 2 ) ( Wang et al, 2015b ).…”

Section: Introductionmentioning

confidence: 99%

“…Histone acetylation also plays an important role in the cholesterol metabolism of macrophages ( Zubair et al, 2021 ). Alterations in SIRT1 and SIRT6 promote cholesterol efflux by activating ABCA-1 and ATP-binding cassette subfamily G member (ABCG-1), leading to reduced macrophage-derived foam cell formation ( D'Onofrio et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

New Insight in HDACs: Potential Therapeutic Targets for the Treatment of Atherosclerosis

et al. 2022

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Atherosclerosis (AS) features include progressive hardening and reduced elasticity of arteries. AS is the leading cause of morbidity and mortality. An increasing amount of evidence showed that epigenetic modifications on genes serve are a main cause of several diseases, including AS. Histone deacetylases (HDACs) promote the deacetylation at lysine residues, thereby condensing the chromatin structures and further inhibiting the transcription of downstream genes. HDACs widely affect various physiological and pathological processes through transcriptional regulation or deacetylation of other non-histone proteins. In recent years, the role of HDACs in vascular systems has been revealed, and their effects on atherosclerosis have been widely reported. In this review, we discuss the members of HDACs in vascular systems, determine the diverse roles of HDACs in AS, and reveal the effects of HDAC inhibitors on AS progression. We provide new insights into the potential of HDAC inhibitors as drugs for AS treatment.

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“…Thus, there is growing evidence indicating that priming signals such as pathogens and diseases activate the memory of extracellular traps (ETs) and potently increase ETs release in response to a second stimulation. The positive or enhanced response has been coined trained immunity (also known as innate immune memory), which can produce an enhanced immune response against secondary infection of related or unrelated pathogens [ 10 , 11 ]. The resulting immune enhancement is manifested as the enhanced ability of phagocytosis and increased production of cytokines [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular trap can be trained as a memory response

et al. 2022

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Extracellular trap (ET) appears as a double-edged sword for the host since it participates in host immune defense by entrapping pathogens, while excessive ET release also contributes to various diseases progression including atherosclerosis, cancer, and autoimmune disorders. A better understanding of ET formation and regulation will be beneficial for developing strategies for infection control and ET-associated disease treatment. There is some evidence indicating that prior infection can enhance extracellular killing. Neutrophils from cancer or sepsis are predisposed to generate ET. It is reasonable to suspect that ET may be trained to form as a memory response, just like cytokine memory response termed “trained immunity.” The mice were intraperitoneally injected with heat-killed Candida albicans (HK- C. albicans ), 3 days later bone marrow-derived macrophages (BMDM) were isolated and challenged with Clostridium perfringens as a second stimulation. We found that HK- C. albicans priming enhanced ET formation upon Clostridium perfringens infection, accompanied by increased extracellular killing capacity. Mannan priming also enhanced ET formation. Since ETs memory was induced in chicken PBMC, ETs memory may be evolutionarily conserved. Moreover, mTOR was required for ETs memory response. Collectively, this study showed that ETs can be trained as a memory response and indicated that memory property of ETs should be considered during the understanding of recurrent infection and ET-associated disorders.

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Two Faces of Macrophages: Training and Tolerance

Cited by 26 publications

References 161 publications

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

New Insight in HDACs: Potential Therapeutic Targets for the Treatment of Atherosclerosis

Extracellular trap can be trained as a memory response

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