DNA Methylation Patterns in the <i>HLA-DPB1</i> and <i>PDCD1LG2</i> Gene Regions in Patients with Autoimmune Thyroiditis from Different Water Iodine Areas

Wan, Siyuan; Liu, Lixiang; Ren, Bingxuan; Qu, Mengying; Wu, Hui; Jiang, Wen; Wang, Xiaoming; Shen, Hongmei

doi:10.1089/thy.2021.0221

Cited by 11 publications

(9 citation statements)

References 12 publications

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“…In this study, compared with the control group, the expression of PD‐L1 mRNA and PD‐L2 mRNA in the whole blood of mice in the SAT group was significantly increased; the expression of PD‐L2 mRNA was significantly increased; the PD‐1 protein in the thyroid tissue was upregulated in the SAT group; in addition, flow cytometry results showed that the surface PD‐L1 and PD‐L2 of CD3+CD4+ T cells and CD3+CD8+ T cells in the whole blood of mice in the SAT group were significantly higher than those in the control group, suggesting that PD‐1/PD‐L1/PD‐L2 overexpression may be involved in the pathogenesis of SAT, which is consistent with previous research on autoimmune diseases 22–25 . During the pathogenesis of autoimmune diseases, there is a high expression of PD‐1/PD‐L , and the expression of PD‐L2 in whole blood is increased in the SAT group, which is consistent with the results of our previous population research 11 …”

Section: Discussionsupporting

confidence: 91%

“…However, the role of PD‐1/PD‐L in the occurrence and development of AIT is still uncertain. According to our previous 850 k chip methylation sequencing of AIT cases and healthy people in iodine deficient and iodine excess areas, 11 there were differences in the methylation levels of PDCD1LG2_1 and multiple CpG sites in the target region of the PD‐L2 gene, and further verification studies also found that the relative expression levels of PD‐L2 mRNA in AIT cases were higher than those in healthy controls, and there was a negative correlation between them, suggesting that PD‐L2 was involved in the occurrence and development of the disease.…”

Section: Introductionmentioning

confidence: 99%

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A study of programmed death‐1/programmed death ligand and iodine‐induced autoimmune thyroiditis in NOD.H‐2h4 mice

Li,

Zhou,

Wang

et al. 2023

Environmental Toxicology

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Excess iodine will trigger the occurrence of autoimmune thyroiditis (AIT), and programmed death‐1 (PD‐1)/programmed death ligand (PD‐L) will also contribute to the development of AIT. The purpose of this study was to explore the role that negative regulatory signals mediated by PD‐1/PD‐L play in the development of spontaneous autoimmune thyroiditis (SAT) in NOD.H‐2h4 mice when they are exposed to iodine. Programmed death ligand 1 (PD‐L1) antibody was administered intraperitoneally to NOD.H‐2h4 mice. The relevant indicators were determined by flow cytometry, real‐time quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, immunohistochemistry, pathological hematoxylin and eosin staining, and arsenic–cerium catalytic spectrophotometry. Results showed that the level of urinary iodine, the level of thyroid lymphocyte infiltration, the level of thyroglobulin antibodies (TgAb) and interferon (IFN‐γ)/tumor necrosis factor (TNF‐α)/interleukin (IL‐2)/IL‐17, and the relative expression of PD‐1/PD‐L1/programmed death‐2 (PD‐L2) increased with the intervention of excess iodine. After the intervention of the PD‐L1 antibody, the expression of PD‐1/PD‐L1/PD‐L2 in different degrees was inhibited, but the level of thyroid lymphocyte infiltration and serum TgAb/IFN‐γ/TNF‐α/ IL‐2/IL‐17 did not decrease. Collectively, although PD‐1/PD‐L participates in the occurrence of SAT and induces inflammation, administration of the PD‐L1 antibody does not effectively improve the pathological process of SAT. More research is needed to determine whether PD‐1/PD‐L intervention can treat autoimmune thyroid disease.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

A study of programmed death‐1/programmed death ligand and iodine‐induced autoimmune thyroiditis in NOD.H‐2h4 mice

Li,

Zhou,

Wang

et al. 2023

Environmental Toxicology

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“…According to the previous Illumina 850k DNA methylation chip analysis results of our research group, which was performed on ten AIT patients and ten matched controls (27) , we found the methylation differences of several apoptotic function-related genes between AIT cases and healthy controls. In combination with searching related literature, we finally chose the following five extrinsic apoptotic signalling pathway-related genes as the candidate genes: DAPK1, TNFAIP8, TNF superfamily member 8 (TNFSF8), homeobox A5 (HOXA5) and PF4.…”

Section: Selection Of Candidate Genes and Dna Methylation Analysismentioning

confidence: 81%

The whole blood DNA methylation patterns of extrinsic apoptotic signalling pathway-related genes in autoimmune thyroiditis among areas with different iodine levels

Wan

et al. 2022

Br J Nutr

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Autoimmune thyroiditis (AIT) has a complex etiology and the susceptibility to it is determined by a combination of genetic and environmental factors, although these are not yet fully understood. The present research aimed to explore the DNA methylation patterns in whole blood of extrinsic apoptotic signaling pathway related genes in AIT among areas with different iodine levels. We selected the iodine-fortification areas (IFA), iodine-adequate areas (IAA) and water-based iodine-excess areas (IEA) from Shandong Province of China as survey sites. Totally 176 AIT cases and 176 controls were included. MethylTargetTM and QT-PCR technology were used to detect candidate genes’ DNA methylation levels and mRNA expression levels, respectively. We found that DAPK1 DNA methylation levels in AIT cases (especially in female) were significantly higher than controls (t=2.7715, P=0.0059; t=2.4638, P=0.0143 in female). There were differences in DAPK1(t=2.5384, P=0.0121), TNFSF8(t=2.1667, P=0.0334) and TNFAIP8(t=2.5672, P=0.0121) genes methylation between cases and controls with different water iodine levels. The mRNA expression of DAPK1(t=4.329, P<0.001) and TNFAIP8(t=3.775, P<0.001) in the cases were increased. We identified the differences in the DNA methylation status of the extrinsic apoptotic signaling pathway related genes between AIT and controls and in different iodine levels areas. The results were verified at the mRNA level. The environmental iodine may affect DNA methylation to some extent.

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“…These colorectal cancer responsible genes might be candidate genes for CD. Recently, increasing evidence demonstrated that CXCL5 [379], S100A8 [380], LCN2 [381], CXCL1 [382], S100A9 [383], CXCL9 [384], CXCL11 [385], CXCL10 [386], NCF2 [387], SLC11A1 [388], GDF15 [389], IL1RN [390], STAT1 [391], CYP27B1 [392], SOCS3 [393], TLR8 [394], CD55 [395], ADGRG3 [396], CCL3 [397], FCGR2A [398], CCL2 [399], CD14 [400], IGFBP2 [401], PCSK9 [402], IDO1 [403], FOXP3 [404], CD163 [405], CCL7 [406], TLR2 [407], CCR2 [408], IL20RA [409], S100P [410], ADAMTS1 [411], TIMP1 [412], ICAM1 [413], IFNG (interferon gamma) [414], TREM2 [415], APOE (apolipoprotein E) [416], CCR1 [417], IL6 [418], CTHRC1 [419], PDCD1LG2 [420], CCL4 [421], IL11 [422], COL1A1 [423], MMP2 [424], IL1A [425], CD24 [426], POSTN (periostin) [427], GZMB (granzyme B) [428], BCL2A1 [429], CSF2 [430], TDO2 [431], CTLA4 [432], PADI4 [433], MPO (myeloperoxidase) [434], HP (haptoglobin) [435], MUC5B [436], MMP7 [437], PON3 [438], ABHD6 [439], AICDA (activation induced cytidine deaminase) [440], UGT1A6 [441], CYP2D6 [442], CYP3A5 [443], DGAT1 [444], FCRL4 [445], SLC22A4 [446], DPP4 [447], ACE (angiotensin I converting enzyme) [448], SLC5A11 [449], VIPR1 [450], FCRL3 [451], CD160 [452] and IL22RA2 […”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Pediatric Crohn's Disease (CD) also known as inflammatory bowel diseases, affects millions of people all over the world. The aim of this investigation is to identify the key genes in CD and uncover their potential functions. We downloaded the next generation sequencing (NGS) dataset GSE73374 from the Gene Expression Omnibus (GEO) database. The NGS dataset GSE73374 was used to screen differentially expressed genes (DEGs) between samples from patients with CD and healthy controls. Gene ontology (GO) and REACTOME pathway enrichment analyses were applied for the DEGs. Subsequently, a protein - protein interaction (PPI) network, modules, miRNA- hub gene regulatory network and TF - hub gene regulatory network were constructed to identify hub genes, miRNAs and TFs. Receiver operating characteristic curve (ROC) analysis was applied to validate the hub genes. A total of 957 DEGs were identified, including 478 up regulated genes and 479 down regulated genes. GO and REACTOME results suggested that several Go terms and pathways are involved in response to stimulus, extracellular region, signaling receptor binding, small molecule metabolic process, membrane, transporter activity, immune system and biological oxidations. The top centrality hub genes MDFI, MNDA, FBXO6, TFRC, STAT1, DPP4, MME, SLC39A4, APOA1 and TMEM25 were screened out as the critical genes among the DEGs from the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation identified key genes and signal pathways, which might help us improve our understanding of the molecular mechanisms of CD and identify some novel therapeutic targets for CD.

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DNA Methylation Patterns in the HLA-DPB1 and PDCD1LG2 Gene Regions in Patients with Autoimmune Thyroiditis from Different Water Iodine Areas

Cited by 11 publications

References 12 publications

A study of programmed death‐1/programmed death ligand and iodine‐induced autoimmune thyroiditis in NOD.H‐2h4 mice

A study of programmed death‐1/programmed death ligand and iodine‐induced autoimmune thyroiditis in NOD.H‐2h4 mice

The whole blood DNA methylation patterns of extrinsic apoptotic signalling pathway-related genes in autoimmune thyroiditis among areas with different iodine levels

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

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