Implications the Role of miR-155 in the Pathogenesis of Autoimmune Diseases

Pashangzadeh, Salar; Motallebnezhad, Morteza; Vafashoar, Fatemeh; Khalvandi, Azadeh; Mojtabavi, Nazanin

doi:10.3389/fimmu.2021.669382

Cited by 42 publications

(29 citation statements)

References 170 publications

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“…Regarding T-cells, miR-155 seems to control phenotype activation, with a great impact on autoimmune pathology but also bearing relevance to AD. The miR-155 level is essential for T helper cell phenotype induction, with research demonstrating miR-155 deficiency to be correlated with Th2 cell as the dominant phenotype, while miRNA overexpression promotes the Th1 phenotype [ 53 ]. In addition, other types of cells considered to have immune functions, such as dendritic cells and macrophages, are fine-tuned by miR-155.…”

Section: Research Directions Investigating Hhv-6 Involvement In Alzhe...mentioning

confidence: 99%

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

Romanescu

Schreiner

Mukovozov

2022

JCM

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Alzheimer’s disease (AD), a neurodegenerative disorder generally affecting older adults, is the most common form of dementia worldwide. The disease is marked by severe cognitive and psychiatric decline and has dramatic personal and social consequences. Considerable time and resources are dedicated to the pursuit of a better understanding of disease mechanisms; however, the ultimate goal of obtaining a viable treatment option remains elusive. Neurodegenerative disease as an outcome of gene–environment interaction is a notion widely accepted today; a clear understanding of how external factors are involved in disease pathogenesis is missing, however. In the case of AD, significant effort has been invested in the study of viral pathogens and their role in disease mechanisms. The current scoping review focuses on the purported role HHV-6 plays in AD pathogenesis. First, early studies demonstrating evidence of HHV-6 cantonment in either post-mortem AD brain specimens or in peripheral blood samples of living AD patients are reviewed. Next, selected examples of possible mechanisms whereby viral infection can directly or indirectly contribute to AD pathogenesis are presented, such as autophagy dysregulation, the interaction between miR155 and HHV-6, and amyloid-beta as an antimicrobial peptide. Finally, closely related topics such as HHV-6 penetration in the CNS, HHV-6 involvement in neuroinflammation, and a brief discussion on HHV-6 epigenetics are examined.

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Section: Research Directions Investigating Hhv-6 Involvement In Alzhe...mentioning

confidence: 99%

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

Romanescu

Schreiner

Mukovozov

2022

JCM

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“…In conformity, a lower ability to immunoregulate their targets in the recipient cells and a compromised inflammatory response in a pathological circumstance are expected to occur due to the reduced levels of miR-155 in the secretome. Such dysregulation, previously found in our laboratory in sEVs from ALS cortical and spinal astrocytes, may compromise the brain immune system [ 121 ]. Clarification of these findings requires further studies in ALS human models using tricultures of neurons, astrocytes and microglia, spheroids, or organoids.…”

Section: Discussionmentioning

confidence: 89%

Neurotoxic Astrocytes Directly Converted from Sporadic and Familial ALS Patient Fibroblasts Reveal Signature Diversities and miR-146a Theragnostic Potential in Specific Subtypes

Gomes

Sequeira

Likhite

et al. 2022

Cells

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A lack of stratification methods in patients with amyotrophic lateral sclerosis (ALS) is likely implicated in therapeutic failures. Regional diversities and pathophysiological abnormalities in astrocytes from mice with SOD1 mutations (mSOD1-ALS) can now be explored in human patients using somatic cell reprogramming. Here, fibroblasts from four sporadic (sALS) and three mSOD1-ALS patients were transdifferentiated into induced astrocytes (iAstrocytes). ALS iAstrocytes were neurotoxic toward HB9-GFP mouse motor neurons (MNs) and exhibited subtype stratification through GFAP, CX43, Ki-67, miR-155 and miR-146a expression levels. Up- (two cases) and down-regulated (three cases) miR-146a values in iAstrocytes were recapitulated in their secretome, either free or as cargo in small extracellular vesicles (sEVs). We previously showed that the neuroprotective phenotype of depleted miR-146 mSOD1 cortical astrocytes was reverted by its mimic. Thus, we tested such modulation in the most miR-146a-depleted patient-iAstrocytes (one sALS and one mSOD1-ALS). The miR-146a mimic in ALS iAstrocytes counteracted their reactive/inflammatory profile and restored miR-146a levels in sEVs. A reduction in lysosomal activity and enhanced synaptic/axonal transport-related genes in NSC-34 MNs occurred after co-culture with miR-146a-modulated iAstrocytes. In summary, the regulation of miR-146a in depleted ALS astrocytes may be key in reestablishing their normal function and in restoring MN lysosomal/synaptic dynamic plasticity in disease sub-groups.

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“…The findings suggest that the hepatic expression of miR-155 in autoimmune hepatitis is particularly associated with immune-mediated liver injury. This possibility is supported by the implication of miR-155 in the pathogenesis of other autoimmune diseases (207). The discrepancy between serum and tissue levels may reflect active mobilization of miR-155 from the circulation to the liver.…”

Section: Mirna Profilesmentioning

confidence: 93%

Epigenetic Aspects and Prospects in Autoimmune Hepatitis

Czaja¹

2022

Front. Immunol.

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The observed risk of autoimmune hepatitis exceeds its genetic risk, and epigenetic factors that alter gene expression without changing nucleotide sequence may help explain the disparity. Key objectives of this review are to describe the epigenetic modifications that affect gene expression, discuss how they can affect autoimmune hepatitis, and indicate prospects for improved management. Multiple hypo-methylated genes have been described in the CD4+ and CD19+ T lymphocytes of patients with autoimmune hepatitis, and the circulating micro-ribonucleic acids, miR-21 and miR-122, have correlated with laboratory and histological features of liver inflammation. Both epigenetic agents have also correlated inversely with the stage of liver fibrosis. The reduced hepatic concentration of miR-122 in cirrhosis suggests that its deficiency may de-repress the pro-fibrotic prolyl-4-hydroxylase subunit alpha-1 gene. Conversely, miR-155 is over-expressed in the liver tissue of patients with autoimmune hepatitis, and it may signify active immune-mediated liver injury. Different epigenetic findings have been described in diverse autoimmune and non-autoimmune liver diseases, and these changes may have disease-specificity. They may also be responses to environmental cues or heritable adaptations that distinguish the diseases. Advances in epigenetic editing and methods for blocking micro-ribonucleic acids have improved opportunities to prove causality and develop site-specific, therapeutic interventions. In conclusion, the role of epigenetics in affecting the risk, clinical phenotype, and outcome of autoimmune hepatitis is under-evaluated. Full definition of the epigenome of autoimmune hepatitis promises to enhance understanding of pathogenic mechanisms and satisfy the unmet clinical need to improve therapy for refractory disease.

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Implications the Role of miR-155 in the Pathogenesis of Autoimmune Diseases

Cited by 42 publications

References 170 publications

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

The Role of Human Herpesvirus 6 Infection in Alzheimer’s Disease Pathogenicity—A Theoretical Mosaic

Neurotoxic Astrocytes Directly Converted from Sporadic and Familial ALS Patient Fibroblasts Reveal Signature Diversities and miR-146a Theragnostic Potential in Specific Subtypes

Epigenetic Aspects and Prospects in Autoimmune Hepatitis

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