Whole exome sequencing identified a novel splice donor site variant in interleukin 2 receptor alpha chain
AbstractInterleukin 2 receptor alpha chain (IL-2R α or CD25) deficiency (OMIM #606367) is an immune dysregulation disorder segregating in autosomal recessive form. The disease is caused by biallelic variants in theIL-2Rα gene encoding IL-2Rα also known as CD25 protein. IL-2Rα combines with γ and β chains of interleukin 2 receptor to form a functional interleukin 2 receptor (IL-2R). In the present study, we identified a Pakistani family presenting a unique presentation of IL-2Rα deficiency. Clinical whole exo me sequencing revealed a novel splice donor site variant (NM_001378789.1 (NP_001365718); c.64 + 1G >...
Source: Immunogenetics - October 4, 2022 Category: Genetics & Stem Cells Source Type: research
SNHG3 regulates NEIL3 via transcription factor E2F1 to mediate malignant proliferation of hepatocellular carcinoma
This study attempted to deeply investigate the molecular regulatory mechanism of SNHG3 on malignant progression of hepatocellular carcinoma (HCC). According to TCGA analysis, high SNHG3 expression was a risk factor for poor prognosis of HCC patients. Therefore, we further detected the mRNA level of SNHG3 in HCC tissue and cells. It was found that SNHG3 was upregulated in HCC tissue and cells. Afterwards, CCK-8 and flow cytometry assays further proved that silencing SNHG3 inhibited HCC cell proliferation while inducing cell apoptosis and G0/G1 phase arrest. It was also attested in vivo experiments that silencing SNHG3 could...
Source: Immunogenetics - September 17, 2022 Category: Genetics & Stem Cells Source Type: research
Mutated Pkhd1 alone is sufficient to cause autoimmune biliary disease on the nonobese diabetic (NOD) genetic background
AbstractWe previously reported that nonobese diabetic (NOD) congenic mice (NOD.c3c4 mice) developed an autoimmune biliary disease (ABD) with similarities to human primary biliary cholangitis (PBC), including anti-mitochondrial antibodies and organ-specific biliary lymphocytic infiltrates. We narrowed the possible contributory regions in a novel NOD.Abd3 congenic mouse to a B10 congenic region on chromosome 1 ( “Abd3”) and a mutatedPkhd1 gene (Pkhd1del36 −67) upstream fromAbd3, and we showed via backcrossing studies that the NOD genetic background was necessary for disease. Here, we show that NOD.Abd3 mice develop ant...
Source: Immunogenetics - September 13, 2022 Category: Genetics & Stem Cells Source Type: research
IL4I1 enhances PD-L1 expression through JAK/STAT signaling pathway in lung adenocarcinoma
AbstractLung adenocarcinoma (LUAD) is the major type of lung cancer and is one of the deadliest cancers worldwide. IL4I1, as a gene associated with unsatisfactory prognosis, is involved in tumor immune escape, but its immune regulatory mechanism in LUAD is limited. Bioinformatics analysis was applied to analyze the differentially expressed mRNAs and enriched signaling pathways in LUAD tissue. Quantitative real-time polymerase chain reaction (qRT-PCR) was manipulated to test IL4I1 expression. We carried out several methods to examine cell functions: CCK-8 to measure LUAD cell proliferation; flow cytometry to determine cell ...
Source: Immunogenetics - September 3, 2022 Category: Genetics & Stem Cells Source Type: research
Functional consequences of allotypic polymorphisms in human immunoglobulin G subclasses
AbstractHeritable polymorphisms within the human IgG locus, collectively termed allotypes, have often been linked by statistical associations, but rarely mechanistically, to a wide range of disease states. One potential explanation for these associations is that IgG allotype alters host cell receptors ’ affinity for IgG, dampening or enhancing an immune response depending on the nature of the change and the receptors. In this work, a panel of allotypic antibody variants were evaluated using multiplexed, label-free biophysical methods and cell-based functional assays to determine what effect, if any, human IgG polymorphis...
Source: Immunogenetics - July 29, 2022 Category: Genetics & Stem Cells Source Type: research
Oncogenic signaling pathway mediated by Notch pathway-related genes induces immunosuppression and immunotherapy resistance in hepatocellular carcinoma
AbstractThe Notch pathway is a highly conserved signaling pathway involved in the regulation of cell proliferation and differentiation. However, the relationships between Notch pathway-related genes (NPRGs), immunosuppression, and immunotherapy resistance of hepatocellular carcinoma (HCC) remain unclear. Gene expression data and clinical information were extracted from GSE14520, GSE36376, GSE76427, LIRI-JP, TCGA-LIHC, GSE20140, GSE27150, and IMvigor210 datasets. A consensus clustering analysis based on 10 NPRGs was performed to determine the molecular subtypes, and then a notchScore was constructed based on differentially ...
Source: Immunogenetics - July 27, 2022 Category: Genetics & Stem Cells Source Type: research
A highly diverse set of novel immunoglobulin-like transcript (NILT) genes in zebrafish indicates a wide range of functions with complex relationships to mammalian receptors
AbstractMultiple novel immunoglobulin-like transcripts (NILTs) have been identified from salmon, trout, and carp. NILTs typically encode activating or inhibitory transmembrane receptors with extracellular immunoglobulin (Ig) domains. Although predicted to provide immune recognition in ray-finned fish, we currently lack a definitive framework of NILT diversity, thereby limiting our predictions for their evolutionary origin and function. In order to better understand the diversity of NILTs and their possible roles in immune function, we identified five NILT loci in the Atlantic salmon (Salmo salar) genome, defined 86 NILT Ig...
Source: Immunogenetics - July 23, 2022 Category: Genetics & Stem Cells Source Type: research
