MEF2 Is an In Vivo Immune-Metabolic Switch

Clark, Rebecca I.; Tan, Si Heng Sharon; Péan, Claire B.; Roostalu, Urmas; Vivancos, Valérie; Bronda, Kévin; Pilátová, Martina; Fu, Jingqi; Walker, David W.; Berdeaux, Rebecca; Geissmann, Frédéric; Dionne, Marc S.

doi:10.1016/j.cell.2013.09.007

Cited by 149 publications

(138 citation statements)

References 86 publications

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“…In addition, MEF2C is found to be highly expressed in B cells of the spleen and lymph node (Swanson et al 1998), and plays a critical role in B cell proliferation upon antigen stimulation (Khiem et al 2008;Wilker et al 2008). Recently, MEF2 is reported to be a central transcriptional component of the innate immune response in the adult fly (Clark et al 2013). …”

Section: Mef2cmentioning

confidence: 99%

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Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

Zhang

et al. 2015

Arch. Immunol. Ther. Exp.

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Alzheimer's disease (AD) is a complex agerelated neurodegenerative disorder of the central nervous system. Since the first description of AD in 1907, many hypotheses have been established to explain its causes. The inflammation theory is one of them. Pathological and biochemical studies of brains from AD individuals have provided solid evidence of the activation of inflammatory pathways. Furthermore, people with long-term medication of anti-inflammatory drugs have shown a reduced risk to develop the disease. After three decades of genetic study in AD, dozens of loci harboring genetic variants influencing inflammatory pathways in AD patients has been identified through genome-wide association studies (GWAS). The most well-known GWAS risk factor that is responsible for immune response and inflammation in AD development should be APOE e4 allele. However, a growing number of other GWAS risk AD candidate genes in inflammation have recently been discovered. In the present study, we try to review the inflammation in AD and immunity-associated GWAS risk genes like HLA-DRB5/DRB1, INPP5D, MEF2C, CR1, CLU and TREM2.

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Section: Mef2cmentioning

confidence: 99%

“…Recently, MEF2 is reported to be a central transcriptional component of the innate immune response in the adult fly (Clark et al 2013). Therefore, it is a plausible possibility that MEF2 is also involved in the inflammatory process in the brains of individuals with AD through maybe regulating microglia proliferation (Fig.…”

Section: Mef2cmentioning

confidence: 99%

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

Zhang

et al. 2015

Arch. Immunol. Ther. Exp.

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“…[8][9][10][11][12] Exposure of macrophages to bacterial lipopolysaccharide activates the M1 inflammatory phenotype, whereas exposure to interleukin (IL)-4 favors the M2 anti-inflammatory phenotype. 13 In human monocyte-derived macrophages, IRF2BP2 mRNA levels are elevated in the M2 state, but are suppressed to nearly undetectable levels in the M1 state 14 (Geoprofiles, GDS2430:224570_s_at), suggesting that IRF2BP2 may be involved in macrophage polarization.…”

Section: Irf2bp2 Reduces Macrophage Inflammation and Susceptibility Tmentioning

confidence: 99%

IRF2BP2 Reduces Macrophage Inflammation and Susceptibility to Atherosclerosis

Chen

Keyhanian

Zhou

et al. 2015

Circulation Research

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Rationale: Inflammation impairs macrophage cholesterol clearance from vascular tissues and promotes atherosclerosis. Inflammatory macrophages suppress expression of the transcription cofactor interferon regulatory factor 2–binding protein 2 (IRF2BP2), and genetic variants near IRF2BP2 associate with ischemic heart disease progression in humans. Objectives: To test whether IRF2BP2 in macrophages affects atherosclerosis in mice and humans. Methods and Results: We generated mice that delete IRF2BP2 in macrophages. IRF2BP2-deficient macrophages worsened atherosclerosis in irradiated low-density lipoprotein receptor null-recipient mice and in apolipoprotein E null mice. IRF2BP2-deficient macrophages were inflammatory and had impaired cholesterol efflux because of their inability to activate the cholesterol transporter ABCA1 in response to cholesterol loading. Their expression of the anti-inflammatory transcription factor Krüppel-like factor 2 was markedly reduced. Promoter studies revealed that IRF2BP2 is required for MEF2-dependent activation of Krüppel-like factor 2. Importantly, restoring Krüppel-like factor 2 in IRF2BP2-deficient macrophages attenuated M1 inflammatory and rescued M2 anti-inflammatory gene activation and improved the cholesterol efflux deficit by restoring ABCA1 activation in response to cholesterol loading. In a cohort of 1066 angiographic cases and 1011 controls, homozygous carriers of a deletion polymorphism (rs3045215) in the 3′ untranslated region sequence of human IRF2BP2 mRNA had a higher risk of coronary artery disease (recessive model, odds ratio [95% confidence interval]=1.560 [1.179–2.065], P =1.73E-03) and had lower IRF2BP2 (and Krüppel-like factor 2) protein levels in peripheral blood mononuclear cells. The effect of this deletion polymorphism to suppress protein expression was confirmed in luciferase reporter studies. Conclusion: Ablation of IRF2BP2 in macrophages worsens atherosclerosis in mice, and a deletion variant that lowers IRF2BP2 expression predisposes to coronary artery disease in humans.

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“…Moreover, the inability to maintain balance of these functions can lead to chronic inflammation and disease, and organismal ageing is thought to be due to the loss of both metabolic and immune homeostasis. As such, the interplay between metabolic and immune pathways is an area of intense study and a growing number of genes, including foxo, MyD88, TGF-b, mef2, atf3 have been shown in a variety of insects and mammals to function in both metabolism and immunity [105][106][107][108][109][110][111].…”

Section: Expanding Functions For Amps: Beyond Traditional Immune Rolesmentioning

confidence: 99%

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila –microbe interactions

Broderick

2016

Phil. Trans. R. Soc. B

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One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Drosophila melanogaster lives, breeds and feeds on fermenting fruit, an environment that supports a high density, and often a diversity, of microorganisms. This association with such dense microbe-rich environments has been proposed as a reason that D. melanogaster evolved a diverse and potent antimicrobial peptide (AMP) response to microorganisms, especially to combat potential pathogens that might occupy this niche. Yet, like most animals, D. melanogaster also lives in close association with the beneficial microbes that comprise its microbiota, or microbiome, and recent studies have shown that antimicrobial peptides (AMPs) of the epithelial immune response play an important role in dictating these interactions and controlling the host response to gut microbiota. Moreover, D. melanogaster also eats microbes for food, consuming fermentative microbes of decaying plant material and their by-products as both larvae and adults. The processes of nutrient acquisition and host defence are remarkably similar and use shared functions for microbe detection and response, an observation that has led to the proposal that the digestive and immune systems have a common evolutionary origin. In this manner, D. melanogaster provides a powerful model to understand how, and whether, hosts differentiate between the microbes they encounter across this spectrum of associations.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

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MEF2 Is an In Vivo Immune-Metabolic Switch

Cited by 149 publications

References 86 publications

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

IRF2BP2 Reduces Macrophage Inflammation and Susceptibility to Atherosclerosis

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila –microbe interactions

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