Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

Ciferská, Hana; Honsová, Eva; Lodererová, Alena; Hrušková, Zdenka; Neprašová, Michaela; Vachek, Jan; Suchánek, Miloslav; Zima, Tomáš; Coppo, Rosanna; Tesař, Vladimı́r; Novák, Jan; Maixnerová, Dita

doi:10.1007/s40620-019-00640-z

Cited by 16 publications

(12 citation statements)

References 22 publications

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“…Our study found that TLR7 expression was enriched in infiltrated CD19 + B cells in kidneys of patients with IgAN (n = 89) and was closely related to kidney function and renal histopathology, indicating that TLR7 expression in B cells is involved in the pathogenesis and progression of IgAN. Ciferska et al recently detected positive staining of TLR7 in kidney of patients with IgAN but did not find direct correlation between TLR7 intensities and clinical parameters, which may be explained by the small sample size (n = 34) and the use of less sensitive technology (i.e., IHC rather than immunofluorescence) (45).…”

Section: Discussionmentioning

confidence: 92%

TLR7 in B cells promotes renal inflammation and Gd-IgA1 synthesis in IgA nephropathy

Zheng¹,

Xie²,

Ye³

et al. 2020

JCI Insight

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Section: Discussionmentioning

confidence: 92%

TLR7 in B cells promotes renal inflammation and Gd-IgA1 synthesis in IgA nephropathy

Zheng¹,

Xie²,

Ye³

et al. 2020

JCI Insight

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“…Activation of TLR9/MyD88 signaling pathway was shown to be associated with severe renal injury in IgAN based on a murine model [25]. In addition, a recent study showed that intrarenal staining of TLR4, 7, 8, and 9 was more intense in IgAN patients than in healthy controls, and the intensity of TLR4 and TLR9 in kidney tissue was associated with disease severity [26]. All these data indicated the involvement of TLRs in IgAN.…”

Section: Discussionmentioning

confidence: 99%

Monozygotic Twins Discordant for Immunoglobulin A Nephropathy Display Differences in DNA Methylation and Gene Expression

et al. 2020

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Introduction: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. It involves both genetic and environmental factors, among which DNA methylation, the most studied epigenetic modification, was shown to play a role. Here, we assessed genome-wide DNA methylation and gene expression profiles in 2 pairs of IgAN-discordant monozygotic (MZ) twins, in order to characterize methylation changes and their potential influences on gene expression in IgAN. Methods: Genome-wide DNA methylation and gene expression profiles were evaluated in peripheral blood mononuclear cells obtained from 2 IgAN-discordant MZ twins. Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were detected, and an integrated analysis was performed. Finally, functional enrichment analysis was done for DMR-associated genes and DEGs. Results: Totally 521 DMRs were detected for 2 IgAN-discordant MZ twins. Among them, 9 DMRs were found to be mapped to genes that differentially expressed in 2 MZ twins, indicating the potential regulatory mechanisms of expression for these 9 genes (MNDA, DYSF, IL1R2, TLR6, TREML2, TREM1, IL32, S1PR5, and ADGRE3) in IgAN. Biological process analysis of them showed that they were mostly involved in the immune system process. Functional enrichment analysis of DEGs and DMR-associated genes both identified multiple pathways relevant to inflammatory and immune responses. And DMR-associated genes were significantly enriched in terms related to T-cell function. Conclusions: Our findings indicate that changes in DNA methylation patterns were involved in the pathogenesis of IgAN. Nine target genes detected in our study may provide new ideas for the exploration of molecular mechanisms of IgAN.

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“…It is widely expressed in immune cells (such as macrophages, dendritic cells, NK cells, lymphocytes, granulocytes) and non-immune cells (such as epithelial cells, endothelial cells, fibroblasts, cancer cells, etc. ), and is involved in almost all human disease processes (Ciferska et al, 2020). Among the 13 TLRs in human or 11 TLRs in mice, TLR4 has been the first to be identified and has a relatively broad ligand specificity.…”

Section: Introductionmentioning

confidence: 99%

TLR4 Deficiency Exacerbates Biliary Injuries and Peribiliary Fibrosis Caused by Clonorchis sinensis in a Resistant Mouse Strain

Yan

et al. 2021

Front. Cell. Infect. Microbiol.

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Mice with different genetic backgrounds have various susceptibilities to infection with Clonorchis sinensis, although the mechanisms underlying are largely unknown. Toll-like receptor 4 (TLR4) as one of the most important pattern recognition receptors (PPRs) is essential for the invasion, survival, pathogenesis, and elimination of worms. The roles played by TLR4 in C. sinensis infection may vary due to the different genetic backgrounds of mice. In the present study, a relatively resistant mouse strain-C57BL/10 to C. sinensis was used for investigation on the possible roles of TLR4 in the biliary injuries and peribiliary fibrosis. TLR4 wild type (TLR4wild) and TLR4 defective (TLR4def) mice were orally infected with 45 metacercariae of C. sinensis, and all C. sinensis-infected mice and non-infected groups were anesthetized on day 28 post-infection. The liver and serum from each mouse were collected for assessment of the biliary injuries and biliary fibrosis. Meanwhile, hepatic leukocytes were isolated and detected for the activation of M1 or M2 macrophage using flow cytometry. The hepatic type 1 immune response and type 2 immune responses -relative molecules were also evaluated using ELISA and quantitative PCR. The data showed that TLR4def aggravated liver inflammatory cell infiltrations, bile duct proliferation, biliary and hepatocellular injuries, and ECM deposition in C. sinensis-infected mice, compared with TLR4wild mice when they were intragastrically administered with the same amounts of C. sinensis metacercaria. Furthermore, the M2-like macrophages and type 2 immune responses were significantly predominant induced in TLR4def mice, compared with that of TLR4wild mice following C. sinensis infection. But the type 1 immune response were significantly decreased in TLR4def mice, compared with TLR4wild mice after C. sinensis infection. These data demonstrate that TLR4 deficiency exacerbates biliary injuries and peribiliary fibrosis caused by C. sinensis in C57BL/10 strain mice, which is contributed by augments of type 2 immune responses and decrease pro-inflammatory responses.

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Does the renal expression of Toll-like receptors play a role in patients with IgA nephropathy?

Cited by 16 publications

References 22 publications

TLR7 in B cells promotes renal inflammation and Gd-IgA1 synthesis in IgA nephropathy

TLR7 in B cells promotes renal inflammation and Gd-IgA1 synthesis in IgA nephropathy

Monozygotic Twins Discordant for Immunoglobulin A Nephropathy Display Differences in DNA Methylation and Gene Expression

TLR4 Deficiency Exacerbates Biliary Injuries and Peribiliary Fibrosis Caused by Clonorchis sinensis in a Resistant Mouse Strain

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