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Autoimmune regulator (Aire) mutations result in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which manifests as multi-organ autoimmunity and chronic mucocutaneous candidiasis (CMC). Indendritic cells (DCs), pattern recognition receptors (PRR), such as Toll-like receptors (TLRs), are closely involved in the recognition of various pathogens, activating the intercellular signaling pathway, followed by the activation of transcription factors and the expression of downstream genes, which take part in mediating the immune response and maintaining immune tolerance. In this study, we found that Aire up-regulated TLR3 expression and modulated the downstream cytokine expression and nuclear factor-κB (NF-κB) of the TLR3 signaling pathway.
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http://dx.doi.org/10.3390/ijms17122002 | DOI Listing |
Sci Rep
August 2025
Department of Medicine, Haukeland University hospital, Bergen, Norway.
Autoimmune Polyendocrine Syndrome Type 1 (APS-I) results from mutations in the Autoimmune Regulator (AIRE) gene and serves as a valuable model to understand autoimmunity and immune deficiency. Various studies have produced differing results on how AIRE dysfunction affects the balance of immune cell subsets in blood in humans. We conducted high-resolution whole blood immune cell subset analysis using a 36-panel mass cytometry assay in Norwegian APS-I patients (N = 18) and compared with age and sex-matched healthy subjects (N = 19).
View Article and Find Full Text PDFMediastinum
June 2025
Department of Pharmacology & Physiology, George Washington University, Washington, DC, USA.
Background And Objective: Thymic pathology is observed in approximately 80% of patients with acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG). Among these thymic abnormalities, thymic follicular hyperplasia (TFH) is commonly associated with early-onset MG (EOMG). TFH is characterized by the presence of lymphoid follicles and germinal center (GC) formation, which are closely linked with the breakdown of tolerance to the AChR.
View Article and Find Full Text PDFbioRxiv
January 2025
Muscle Disease Section, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bethesda, MD, USA.
Objectives: In dermatomyositis patients with anti-Mi2 autoantibodies, autoantibodies can enter muscle cells, leading to the aberrant expression of genes normally repressed by the Mi2/nucleosome remodeling and deacetylation (NuRD) complex. However, the mechanism by which autoantibodies interfere with Mi2/NuRD function remains unclear. This study aimed to identify additional autoantibodies in anti-Mi2-positive patients as well as the specific epitopes recognized by anti-Mi2 and any novel autoantibodies.
View Article and Find Full Text PDFFront Immunol
June 2025
Pathology Section, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Background: The retinoic-acid-receptor-related orphan receptor gamma t (RORγt) isoform is required for the development of lymphoid organs, T-helper 17 cells (Th17), and innate lymphoid cells (ILC3s). Recent data in mouse and human have revealed non-T, non-ILC3 cell populations with antigen presenting features that express RORγt. This study maps the presence of RORγt cells with dendritic cell (DC) features in human adult and fetal lymphoid tissues.
View Article and Find Full Text PDFSci Rep
May 2025
Regional Center of Medical Genetics Timis, Clinical Emergency Hospital for Children "Louis Turcanu", Part of ERN ITHACA, Timisoara, Timis, Romania.
Inborn errors of immunity (IEI) are monogenic disorders with a wide spectrum of clinical phenotypes including immune dysregulation, autoimmunity, autoinflammation, and malignancy. IEI may have life-threatening consequences, thus precise and timely genetic diagnosis is crucial for improved access to treatment, genetic counselling and prevention. We aimed to investigate the genotypic findings in a cohort of children with IEI from Romania, in order to understand the diagnostic yield of genetic testing, genetic characterization of IEI and impact of genetic diagnosis.
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