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Type 1 diabetes (T1D) develops spontaneously despite functional antigen presentation machinery in the thymus and a perceptible central tolerance process. We found that intrathymic enrichment with IL-4 fine tunes signaling through the IL-4/IL-13 heteroreceptor (HR) in early thymic progenitors (ETPs), augments negative selection of self-reactive T cells, sustains a diverse T cell repertoire devoid of clones expressing disease-associated T cell receptor (TCR) genes, and protects the nonobese diabetic (NOD) mouse from T1D. Indeed, optimal IL-4 activates STAT transcription factors to program ETP fate decision toward CD11c+CD8α+ dendritic cells (DCs) agile in negative T cell selection and clonal deletion of diabetogenic T cells.

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Article Synopsis
  • Targeted therapies using biologics for atopic diseases, urticaria, and angioedema are advancing quickly, with several new antibodies developed, tested, and approved for clinical use, like omalizumab and dupilumab.
  • There is ongoing research into combining different biologics for enhanced treatment efficacy, expanding their applications to conditions like food allergies and eosinophilic esophagitis.
  • There are emerging concerns about unexpected side effects and hypersensitivity reactions associated with these therapies, raising important questions about their safety and mechanisms, particularly in specific patient groups like children.
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  • The study identified frequent conditions such as cardiomyopathy, chronic nephropathy, and adrenal cortex hyperplasia among both sexes, with notable differences in prevalence.
  • In male rats, chronic progressive nephropathy (80.9%) and cardiomyopathy (73.2%) were most prevalent, while in females, cystic adrenal degeneration (64.7%) and brain compression from pituitary tumors (62.7%) were common.
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