Roughly one-half of mice with partial defects in two immune tolerance pathways (AireLyn mice) spontaneously develop severe damage to their retinas due to T cell reactivity to Aire-regulated interphotoreceptor retinoid-binding protein (IRBP). Single-cell T cell receptor (TCR) sequencing of CD4 T cells specific for a predominate epitope of IRBP showed a remarkable diversity of autoantigen-specific TCRs with greater clonal expansions in mice with disease. TCR transgenic mice made with an expanded IRBP-specific TCR (P2.U2) of intermediate affinity exhibited strong but incomplete negative selection of thymocytes. This negative selection was absent in IRBP mice and greatly defective in Aire mice. Most P2.U2 mice and all P2.U.2Aire mice rapidly developed inflammation of the retina and adjacent uvea (uveitis). Aire-dependent IRBP expression in the thymus also promoted Treg differentiation, but the niche for this fate determination was small, suggesting differences in antigen presentation leading to negative selection vs. thymic Treg differentiation and a stronger role for negative selection in preventing autoimmune disease in the retina.
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http://dx.doi.org/10.1073/pnas.2311487121 | DOI Listing |
BMC Med Genomics
January 2025
Department of Oncology, The First People's Hospital of Yibin, No.65, Wenxing Street, Cuiping District, Yibin, 644000, China.
Background: Advanced gastric cancer (GC) exhibits a high recurrence rate and a dismal prognosis. Myocyte enhancer factor 2c (MEF2C) was found to contribute to the development of various types of cancer. Therefore, our aim is to develop a prognostic model that predicts the prognosis of GC patients and initially explore the role of MEF2C in immunotherapy for GC.
View Article and Find Full Text PDFBMC Cancer
January 2025
Jiangxi Provincial Key Laboratory of Child Development and Genetics, Jiangxi Provincial Children's Hospital, No. 122 of YangMing Road, DongHu District, NanChang, 330006, China.
Background: Hepatocellular carcinoma (HCC) is a prevalent primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, the 5-year survival rate for individuals undergoing curative resection remains between 10% and 15%. Consequently, identifying molecular targets that specifically inhibit the proliferation and metastasis of HCC cells is critical for improving treatment outcomes.
View Article and Find Full Text PDFObjectives: Nearly 40 000 Italian patients had their arthroplasty postponed between March and May 2020 (lockdown period) and experienced a period of several months without knowing when surgeries would resume. The hypothesis was that such conditions caused changes in perceived well-being and quality of life. The study aimed to explore the feelings, perceptions and concerns of orthopaedic patients in Italy during COVID-related arthroplasty rescheduling.
View Article and Find Full Text PDFJ Control Release
January 2025
State Key Laboratory of Food Science and Resources, China-Canada Joint Lab of Food Science and Technology (Nanchang), Key Laboratory of Bioactive Polysaccharides of Jiangxi Province, Nanchang University, Nanchang 330047, China.
Selenium deficiency associated with a high risk of many diseases remains a global challenge. Owing to the narrow margin between "nutrition-toxicity" doses of selenium, it is imperative to achieve accurate selenium supplement. Nano‑selenium (SeNPs) is a novel form of selenium supplement with low toxicity, but it could be trapped and removed by intestinal mucus, thus limiting its oral delivery.
View Article and Find Full Text PDFProc Biol Sci
January 2025
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907-2054, USA.
Aquatic ecosystems are highly dynamic environments vulnerable to natural and anthropogenic disturbances. High-economic-value fisheries are one of many ecosystem services affected by these disturbances, and it is critical to accurately characterize the genetic diversity and effective population sizes of valuable fish stocks through time. We used genome-wide data to reconstruct the demographic histories of economically important yellow perch () populations.
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