LncRNA MEG3 regulates the interplay between Th17 and Treg cells in Behçet's disease and systemic lupus erythematosus

Mehana, Noha Ali; Ghaiad, Heba R.; Hassan, Mariam; Elsabagh, Yumn A.; Labib, Safa; Abd-Elmawla, Mai A.

doi:10.1016/j.lfs.2022.120965

Cited by 22 publications

(16 citation statements)

References 30 publications

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“…Early evidence has revealed that the interaction between lncRNAs and miRNAs acts as influential and potential modifiers in MS. − Noncoding RNAs have been shown to be involved in diverse processes in the pathogenesis of MS, including immune system regulation and chronic inflammatory responses. , MAGI2 antisense RNA 3 (MAGI2-AS3) (gene ID: 100505881; ensemble; ENSG00000234456) is a novel type of lncRNA comprising 18252 bp, 8 exons and located on chromosome 7q21.11. Databases revealed that MAGI2-AS3 is widely expressed in fats, ovaries, and other tissues and is interrelated with cell proliferation, metastasis, and treatment resistance in several types of cancer. , Furthermore, the association between MAGI2-AS3 and chronic inflammatory diseases, neurotoxicity, and neuro-inflammation has also been reported .…”

Section: Introductionmentioning

confidence: 99%

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MAGI2-AS3 and miR-374b-5p as Putative Regulators of Multiple Sclerosis via Modulating the PTEN/AKT/IRF-3/IFN-β Axis: New Clinical Insights

Kortam

Elfar

Shaker

et al. 2023

ACS Chem. Neurosci.

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Multiple sclerosis (MS) is a chronic disease and one of the leading causes of disability in young adults. The current study aims to investigate the pathogenesis of MS via studying the regulatory role of novel lncRNA MAGI2-AS3 in miR-374b-5p and their downstream targets PTEN/AKT/IRF-3/IFN-β and the relationship of this pathway with disease severity. Moreover, it aims to assess the role of MAGI2-AS3/miR-374b-5p as diagnostic and/or prognostic biomarkers for MS. Overall, 150 contributors were recruited: 100 patients with MS and 50 healthy volunteers. Gene expression of MAGI2-AS3, miR-374b-5p, PTEN, AKT, and IRF-3 were assessed using RT-qPCR, and IFN-β was measured by ELISA. Compared with the healthy control group, serum MAGI2-AS3 and PTEN were downregulated in MS patients, whereas miR-374b-5p, PI3K, AKT, IRF-3, and IFN-β were upregulated in MS patients. Furthermore, MAGI2-AS3 was downregulated, while miR-374b-5p was upregulated in MS patients with an expanded disability status scale (EDSS) ≥3.5, compared to patients with an EDSS <3.5. Receiver-operating-characteristic curve analysis revealed that MAGI2-AS3 and miR-374b-5p can be used in the diagnosis of MS. Remarkably, multivariate logistic analysis revealed that MAGI2-AS3, miR-374b-5p, PTEN, and AKT act as independent variables in MS. Moreover, MAGI2-AS3 was directly correlated with PTEN and inversely correlated with miR-374b-5p, AKT, and EDSS. Regarding miR-374b-5p, it was positively correlated with AKT and EDSS. In conclusion, the study showed for the first time that the crosstalk between MAGI2-AS3 and miR-374b-5p could affect the AKT/IRF3/IFN-β axis in MS. Interestingly, MAGI2-AS3 and miR-374b-5p could be genetic noninvasive biomarkers for MS.

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Section: Introductionmentioning

confidence: 99%

“…Taken as a whole, the absence of robust diagnostic criteria in MS hampers effective treatment . In the last few decades, noncoding RNAs have gained attention as accurate, reproducible, and noninvasive diagnostic and prognostic tools as well as therapeutic targets. , However, their precise role was not fully understood.…”

Section: Introductionmentioning

confidence: 99%

MAGI2-AS3 and miR-374b-5p as Putative Regulators of Multiple Sclerosis via Modulating the PTEN/AKT/IRF-3/IFN-β Axis: New Clinical Insights

Kortam

Elfar

Shaker

et al. 2023

ACS Chem. Neurosci.

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“…They showed the importance of IL23/IL17 pathway in the pathogenesis of uveitis (Chi et al., 2008). Previous studies demonstrated the critical role of IL‐21 in the peripheral blood and inflammatory lesions of patients with active BD by modulating TH17 differentiation and FoxP3 expression (Mehana et al., 2022). Soon after activation, Th17 cells specifically express IL‐21, and autocrine IL‐21 plays an important role in RORγt and IL‐17 expression.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐21 receptor gene polymorphism (rs2285452 A/G) is associated with susceptibility to Behçet's disease

Lahmar

Chabchoub

Zemni

et al. 2023

Int J Immunogenetics

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Behçet's disease (BD) is a chronic auto inflammatory disorder of unknown aetiology.Recently, the dysregulation of interleukin-21 receptor (IL-21R) has been incriminated in different autoimmune and auto-inflammatory diseases, such as systemic lupus erythematous, rheumatoid arthritis, and type 1 diabetes. Herein, we aimed to investigate the association of two Il-21R gene polymorphisms with BD. IL-21R rs2214537 and IL-21R rs2285452 genotypings were investigated in a cohort of 110 adult patients with BD and 116 age and gender unmatched healthy controls. Genotyping was performed by mutagenically separated polymerase chain reaction with newly designed primers. IL-21R rs2285452 genotypes and alleles distribution were statistically different between patients with BD and controls. GA and AA genotypes carrying the minor A allele were more frequent in patients with BD than in healthy controls (37.3% and 11.8% vs. 23.3% and 3.4%, respectively). The minor A allele was associated with an increased BD risk (odds ratios = 2.42, 95% confidence interval = 1.214.87, p = .005).IL-21R rs2214537 GG genotype was found to be associated with susceptibility to BD in the recessive model (GG vs. CC + CG; p = .046, OR = 1.91, 95% CI = 1.003.650. IL-21R rs2285452 and IL-21R rs2214537 were not in linkage disequilibrium (D' = 0.42).The AG haplotype was more frequently observed in patients with BD than in controls (0.247 vs. 0.056, p = .0001). This study for the first time reports the association of IL-21R rs2285452 and IL-21R rs2214537 with BD. Functional studies are required to elucidate the exact role of these genetic variants.

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“…Epigenetic factors are directly involved in regulating the balance of immune cells. Several microRNAs and LncRNAs associated with the Th17/regulatory T cell (Tregs) ratio and differentiation of M1 and M2 macrophages have been identified [25][26][27]. The profile and quantity of these noncoding RNAs are likely to be associated with changes in the pool of immune cells and can be used as additional markers of NAFLD progression, particularly in cases where liver biopsies are needed to assess immune cell balance.…”

Section: Immune Cell Balance As a Possible Marker Of Nafld Progressionmentioning

confidence: 99%

Immune cell balance as potential biomarker of progressing non-alcoholic fatty liver disease

Topchieva,

Kurbatova,

Dudanova

et al. 2024

Genes & Cells

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Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic, slowly progressive metabolic multifactorial disease. It is represented by a number of clinical and morphological forms: steatosis, non-alcoholic steatohepatitis (NASH) (with or without fibrosis) and liver cirrhosis. The search for minimally invasive and cost-effective biomarkers of NAFLD is a key task in the diagnosis, staging of progression, and long-term monitoring of NAFLD. The article discusses the possibility of using the balance of immune cells as potential minimally invasive peripheral markers of NAFLD progression. In the progression of NASH (from steatosis to fibrosis and cirrhosis) an important role is played by inflammation realized due to the activation Kupffer cells, and increased migration of monocytes, dendritic cells, neutrophils, activated T-lymphocytes into the tissues of the organ. Macrophages originating from monocytes, with the progression of NASH, gradually begin to prevail over the pool of resident macrophages. The risk of developing NASH and fibrosis in patients with NAFLD increases with the ratio of neutrophils/lymphocytes in the liver. An increase in the number of Th17 and decrease in Treg cells can contribute to increased hepatic steatosis and the development of inflammation in NAFLD, as well as accelerate the transition from simple steatosis to steatohepatitis and fibrosis.

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LncRNA MEG3 regulates the interplay between Th17 and Treg cells in Behçet's disease and systemic lupus erythematosus

Cited by 22 publications

References 30 publications

MAGI2-AS3 and miR-374b-5p as Putative Regulators of Multiple Sclerosis via Modulating the PTEN/AKT/IRF-3/IFN-β Axis: New Clinical Insights

MAGI2-AS3 and miR-374b-5p as Putative Regulators of Multiple Sclerosis via Modulating the PTEN/AKT/IRF-3/IFN-β Axis: New Clinical Insights

Interleukin‐21 receptor gene polymorphism (rs2285452 A/G) is associated with susceptibility to Behçet's disease

Immune cell balance as potential biomarker of progressing non-alcoholic fatty liver disease

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