No association between transmembrane protein–tyrosine–phosphatase receptor type C (CD45) exon A 77C&gt;G transversion and Hashimoto's thyroiditis in a German population

Thude, Hansjörg; Weissenborn, Soenke J.; Vilser, C; Müller, Ulrich A.; Kloos, C; Wolf, Günter; Beck, James F.; Barz, Dagmar

doi:10.1016/j.humimm.2009.10.010

Cited by 5 publications

(3 citation statements)

References 34 publications

(33 reference statements)

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“…, 58 but the association was not confirmed in subsequent studies 59–62 . The SNP is not associated with type 1 diabetes (T1D), 63,64 Graves’ disease, 63 SLE, 65 Hashimoto’s thyroiditis 66 or myasthenia gravis 67 . An association was found with autoimmune hepatitis, 68 and another study reported an increased frequency of the SNP in systemic sclerosis 69 .…”

Section: Class I Enzymesmentioning

confidence: 98%

Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity

2012

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Activation of T cells is largely mediated through signal transduction downstream from the T-cell receptor (TCR) expressed on the cell surface. The TCR is a transmembrane receptor complex comprised of a and b chains, which bind ligands, and CD3 (e, c and d) and f chains containing motifs that are phosphorylated on tyrosine, called immunoreceptor tyrosine-based activation motifs. Signal transduction through the TCR is initiated when the receptor binds to a peptide-MHC complex presented by an antigen-presenting cell. This interaction initiates a cascade of signalling events, which induces the proliferation, mobilization and differentiation of T cells. For an updated and comprehensive review of signalling through the TCR the reader is referred to recent authoritative publications. [1][2][3][4] A dynamic wave of tyrosine phosphorylation phenomena is critical for ignition of intracellular signalling in T cells. Engagement of the TCR leads to the activation of the Src family protein tyrosine kinases (PTKs) LCK and FYN, which phosphorylate the immunoreceptor tyrosinebased activation motifs of the TCR. This provides docking sites for the SH2 domains of ZAP-70, a Syk family PTK, allowing ZAP-70 to be phosphorylated and activated by LCK. Once activated, ZAP-70 phosphorylates the adaptor proteins SLP-76 and LAT, which nucleate signalling complexes, leading to the phosphorylation and activation of multiple downstream effectors. This results in calcium mobilization, activation of mitogen-activated protein kinases (MAPKs), transcriptional regulation and cytoskeletal rearrangements.Protein tyrosine phosphatases (PTPs) are the natural counterpart of PTKs. Much like PTKs, depending upon the phosphorylation site and the signalling context, they can enhance or reduce the function of their protein target(s). The modern view of phosphorylation networks is one of dynamic 'always-on' grids where the stoichiometry of each phosphorylation site is continuously controlled by the changing balance between the activities of kinases and phosphatases. For example, the activation state of the Src family kinases (SFKs) is balanced between the activities of CSK and CD45, which respectively phosphorylate and dephosphorylate the inhibitory C-terminal site (Y505 of LCK), and the negative regulators LYP and SHP-1, which dephosphorylate an activating tyrosine in the catalytic domain (Y394 of LCK). Acute changes in PTP activity/ expression are in principle sufficient to alter the network status and even trigger true signalling waves. The recent 'kinetic-segregation' model postulates that PTPs are responsible for the very initiation of signalling after engagement of the TCR. SummaryMore than half of the known protein tyrosine phosphatases (PTPs) in the human genome are expressed in T cells, and significant progress has been made in elucidating the biology of these enzymes in T-cell development and function. Here we provide a systematic review of the current understanding of the roles of PTPs in T-cell activation, providing insight into their mechanisms ...

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Section: Class I Enzymesmentioning

confidence: 98%

Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity

2012

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“…PCR of exon A of the PTPRC gene was carried out in a final volume of 40 lL with 200 ng DNA, 25lL PCR Master (Roche, Mannheim, Germany) containing 1.25 U Taq polymerase in 20 mM Tris-HCl, 100 mM KCl, 3 mM MgCl 2 , dNTP mix (dATP, dCTP, dGTP and dTTP each 0.4 mM), and 20 pmol exon A-specific primers (forward, 5¢-ATTTATTTTGTCCTTCTCCCA-3¢ and reverse, 5¢-GTTAACAACTTTTGTGTGCCAAC-3¢). Amplification conditions were described elsewhere (Thude et al, 2010). PCR products were precipitated and subsequently digested with MspI (New England Biolabs GmbH, Frankfurt am Main, Germany), according to the manufacturer's recommendation.…”

Section: Genotyping Of Ptprc Exon a 77c>g Transversionmentioning

confidence: 99%

No association between transmembrane protein‐tyrosine phosphatase receptor type C (PTPRC) exon A 77C>G transversion and liver transplant rejection

Thude

Schipler

Treszl

et al. 2012

Int J Immunogenetics

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This study was carried out to evaluate the association between 77C>G transversion (rs17612648) in exon A of the PTPRC gene and liver transplant rejection. No significant differences in genotype and allele frequencies of the 77C>G transversion were detected between recipients without rejection (n = 106) and recipients with rejection (n = 104). In conclusion, there was no evidence for the contribution of the 77C>G transversion in susceptibility to liver transplant rejection in a Caucasian population.

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“…Hashimoto's thyroiditis (HT), also known as chronic lymphocytic or autoimmune thyroid disease, is the most common inflammatory disease affecting the thyroid gland and the leading cause of primary hypothyroidism, with a prevalence of roughly 5% in the adult population and rising prevalence and incidence [3]. It is considered to be the consequence of an immune response leading to abnormal infiltration of autoantigens including thyroglobulin (TG) and thyroid peroxidase (TPO) specifically in lymphocytes that contribute to the damage to thyroid follicles [4,5]. The exact pathogenesis of Hashimoto's thyroiditis (HT) also has not been fully clarified.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Analysis of the Cross-talk Between Idiopathic Pulmonary Fibrosis and Hashimoto's Thyroiditis on the Hub Genes and Key Pathways

Ding

Kong

et al. 2022

Preprint

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Background: Idiopathic pulmonary fibrosis (IPF) is a disease of unknown cause, and there is increasing evidence that Hashimoto's thyroiditis (HT) is closely related to IPF. However, the mechanism of their interaction relationship remains unclear. The purpose of this study was to explore the common genetic features and underlying molecular and immune mechanisms between HT and IPF. Methods: Microarray data of HT and IPF were obtained from the Gene Expression Omnibus (GEO) database. The R software was used to identify the differential genes between two datasets and take the common differential genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of common DEGs present in HT and IPF using R software. The protein-protein interaction (PPI) network of their DEGs was constructed Utilizing the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) database, identified and visualized hub genes by the Cytoscape software. To further investigate the diagnostic value of the hub genes, the receptor operating characteristic (ROC) curves were constructed utilizing the ‘pROC’ package. Subsequently, ROC analysis in two independent GEO datasets further validates the diagnostic value of these six hub genes. A miRNA-gene interactions network, TF-gene interactions network, and TF-miRNA coregulatory network were constructed by the NetworkAnalyst using hub genes and visualized by the Cytoscape for further analysis. In addition, R software was also applied to analyze immunological infiltration. Results: A total of 572 common DEGs were identified from the two datasets for subsequent analysis, which were primarily enriched in immune and inflammatory-related pathways. The plug-in ‘cytoHubba’ of the Cytoscape software was utilized to recognize six shared hub genes after validation, including CYBB, CD68, CD8A, CCL2, CCL5, and PTPRC. We predicted the miRNAs related to hub genes, including miR-106b-5p, miR-155-5p, miR-98-5p, let-7g-3p, and potential TFs (SPI1, NFKB1, NFKB2) through the interaction network. In addition, immune cell infiltration analysis revealed a significant infiltration of central memory CD4+ T cells infiltration in both IPF and HT samples. Conclusions: Bioinformatics studies reveal the common pathogenesis and immunological features between Hashimoto's thyroiditis and idiopathic pulmonary fibrosis. These common pathways and hub genes may serve as molecular biomarkers for diagnosable as well as prognostic assessment, providing new targets and ideas for further mechanistic studies. Additionally, the immune system plays a crucial role in the initiation and progression of both diseases. Keywords: idiopathic pulmonary fibrosis, Hashimoto's Thyroiditis, hub gene, immune process, bioinformatics

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No association between transmembrane protein–tyrosine–phosphatase receptor type C (CD45) exon A 77C>G transversion and Hashimoto's thyroiditis in a German population

Cited by 5 publications

References 34 publications

Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity

Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity

No association between transmembrane protein‐tyrosine phosphatase receptor type C (PTPRC) exon A 77C>G transversion and liver transplant rejection

Bioinformatics Analysis of the Cross-talk Between Idiopathic Pulmonary Fibrosis and Hashimoto's Thyroiditis on the Hub Genes and Key Pathways

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