Peripheral blood and hepatic Toll-like receptor 7 expression and interferon lambda 1 levels in chronic hepatitis C: Relation to virus replication and liver injury

Aggan, Hoda El; Farahat, Nahla; Deeb, Nader; Zeid, Ahmed; El-Shendidi, Assem

doi:10.1016/j.micpath.2019.03.032

Cited by 3 publications

(5 citation statements)

References 68 publications

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“…One of the immune‐regulatory genes known to escape X chromosomal inactivation codes for Toll‐like receptor 7 (TLR7) 43 . TLR7 represents an endosomal innate immune sensor crucial for recognition of numerous pathogens, including viruses, which activates immune response by participating in a signaling cascade that induces both type I and type III IFNs production 45,46 . Female‐biased TLR7 expression leads to increased level of TLR7 in many tissues, including plasmacytoid dendritic cells, 47 resulting in higher expression of both types of IFNs in females as compared to males 48 .…”

Section: Discussionmentioning

confidence: 99%

“…43 TLR7 represents an endosomal innate immune sensor crucial for recognition of numerous pathogens, including viruses, which activates immune response by participating in a signaling cascade that induces both type I and type III IFNs production. 45,46 Female-biased TLR7 expression leads to increased level of TLR7 in many tissues, including plasmacytoid dendritic cells, 47 resulting in higher expression of both types of IFNs in females as compared to males. 48 In regard to our findings, we believe overexpression of TLR7 in females infected with SARS-CoV-2 might therefore enhance the interplay between type I and type III IFNs, leading to more pronounced protective effect of IFN-λ4 against pneumonia development.…”

Section: Association Between Ifnl4 Polymorphism and The Development O...mentioning

confidence: 99%

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Its all about IFN‐λ4: Protective role of IFNL4 polymorphism against COVID‐19‐related pneumonia in females

Matic,

Milovanovic,

Mijailovic

et al. 2023

Journal of Medical Virology

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Despite the pivotal role of IFN‐λs in the innate immune response, the data on its genetic polymorphism in relation to COVID‐19 severity are scarce and contradictory. In the present study, we aimed to determine if the presence of the most frequent functional single nucleotide polymorphisms (SNPs) of the two most important IFN‐λs coding genes, namely IFNL3 and IFNL4, alters the likelihood of SARS‐CoV‐2‐infected patients to develop more severe form of the disease. This observational cohort study involved 178 COVID‐19 patients hospitalized at the University Clinical Centre Kragujevac, Serbia. Patients' demographics, clinical characteristics, and laboratory parameters were collected at admission. COVID‐19 signs and symptoms were assessed during the hospital stay, with the worst condition determining the disease severity. Genotyping for IFNL3 (rs12980275 and rs8099917) and IFNL4 (rs12979860 and rs368234815) SNPs was conducted using TaqMan assays. Our study revealed carriers of IFNL3 and IFNL4 minor alleles to be less likely to progress from mild to moderate COVID‐19, that is, to develop COVID‐19‐related pneumonia. After adjustment for other factors of influence, such as age, sex, and comorbidities, the likelihood of pneumonia development remained significantly associated with IFNL4 polymorphism (odds ratios [ORs] [95% confidence interval (95% CI)]: 0.233 [0.071; 0.761]). When the patients were stratified according to sex, the protective role of IFNL4 minor alleles, controlled for the effect of comorbidities, remained significant only in females (OR [95% CI]: 0.035 [0.003; 0.408]). Our results strongly suggest that IFNL4 rs12979860 and rs368234815 polymorphisms independently predict the risk of COVID‐19‐related pneumonia development in females.

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Section: Discussionmentioning

confidence: 99%

Section: Association Between Ifnl4 Polymorphism and The Development O...mentioning

confidence: 99%

Its all about IFN‐λ4: Protective role of IFNL4 polymorphism against COVID‐19‐related pneumonia in females

Matic,

Milovanovic,

Mijailovic

et al. 2023

Journal of Medical Virology

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“…The ability of HCV to inhibit the immune response aiming to maintain its persistence has been revealed [13]. Decreased expression of TLR3 and TLR7 in cells infected with HCV via inhibitory effects of HCV proteins aiming to prevent the immune system from clearing the virus has been shown [17,18]. Treatment with IFN-α was used to counteract this effect.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment of mice with the TLR3 ligand poly I:C was shown to inhibit liver fibrogenesis [14][15][16]. Also, TLR7 down-regulation was suggested to contribute to liver fibrosis progression [17].…”

Section: Introductionmentioning

confidence: 99%

Relation between levels of toll-like receptors 3 and 7 and clinical profile of Child-Pugh B cirrhotic patients

Kamal

Ramadan

Sherief

et al. 2021

ceh

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Aim of the study: Growing data show that toll-like receptors (TLRs) have considerable roles in the pathogenesis of many liver diseases. We aimed to study the relation between TLR3 and TLR7 levels and clinical manifestations of liver decompensation among hepatitis C virus (HCV)-infected Child-Pugh B patients. Material and methods: This study included 60 adult patients with Child-Pugh B liver cirrhosis on top of untreated HCV infection. We performed a two-step clustering algorithm depending on TLR-3 gene expression, TLR-7 gene expression, and other influential patients' characteristics. Results: Patients were optimally divided into 2 clusters, each cluster containing 30 patients. The average silhouette score of the clustering algorithm was 0.52, indicating a good clustering power of the model. Patients in cluster 1 showed lower relative expression of TLR3 (0.188 vs. 0.29). The same was true of TLR7 (0.20 vs. 0.31). All patients within cluster 1 had lower limb edema and 93% of them had ascites. On the other hand, no one within cluster 2 had ascites or lower limb edema. The mean platelet count was lower in patients within cluster 1 (74,000 vs. 100,000 cell/mm 3 ). The mean international normalized ratio (INR) level was higher in cluster 1 (1.61 vs. 1.3). The mean Model for End-Stage Liver Disease (MELD) score was higher in cluster 1 (15 vs. 10). Conclusions: From these results, we can suggest that lower TLR3 and TLR7 can lead to worse clinical manifestations among patients with HCV-related liver cirrhosis. A deeper exploration of this point can open the door for new approaches for managing decompensated cirrhosis.

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“…Interestingly, genes downregulated in the miR-124-transduced condition include genes that have been associated with T-cell function and STAT3 regulation such as CCR8 [33], RPTOR [34,35], EED [36], or CYBB [37]. In contrast, genes upregulated in miR-124 expressing cells were mainly associated with inflammation and immune response such as IFNL1 [38], CYP1A1 [39], IL26 [40], CXCL9 [41], and MYD88 [42] (Figure 3B). Additionally, GSEA showed that MYC and E2F target genes were downregulated in miR-124-transduced cells, and these cells display expression dynamics comparable to that observed after miR-21 inhibition in glioma cells [43,44] (Figure 3C).…”

Section: Ectopic Mir-124 Expression In Ctcl Cells Imposes An Altered mentioning

confidence: 99%

Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma

García-Colmenero

González

Sandoval

et al. 2020

Cells

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Increasing evidence supports a potential role for STAT3 as a tumor driver in cutaneous T-cell lymphomas (CTCL). The mechanisms leading to STAT3 activation are not fully understood; however, we recently found that miR-124, a known STAT3 regulator, is robustly silenced in MF tumor-stage and CTCL cells. Objective: We studied here whether deregulation of miR-124 contributes to STAT3 pathway activation in CTCL. Methods: We measured the effect of ectopic mir-124 expression in active phosphorylated STAT3 (p-STAT3) levels and evaluated the transcriptional impact of miR-124-dependent STAT3 pathway regulation by expression microarray analysis. Results: We found that ectopic expression of miR-124 results in massive downregulation of activated STAT3 in different CTCL lines, which resulted in a significant alteration of genetic signatures related with gene transcription and proliferation such as MYC and E2F. Conclusions: Our study highlights the importance of the miR-124/STAT3 axis in CTCL and demonstrates that the STAT3 pathway is regulated through epigenetic mechanisms in these cells. Since deregulated STAT3 signaling has a major impact on CTCL initiation and progression, a better understanding of the molecular basis of the miR-124/STAT3 axis may provide useful information for future personalized therapies.

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Peripheral blood and hepatic Toll-like receptor 7 expression and interferon lambda 1 levels in chronic hepatitis C: Relation to virus replication and liver injury

Cited by 3 publications

References 68 publications

Its all about IFN‐λ4: Protective role of IFNL4 polymorphism against COVID‐19‐related pneumonia in females

Its all about IFN‐λ4: Protective role of IFNL4 polymorphism against COVID‐19‐related pneumonia in females

Relation between levels of toll-like receptors 3 and 7 and clinical profile of Child-Pugh B cirrhotic patients

Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma

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