ArticleThe Journal of clinical investigation2021
NOTCH-induced rerouting of endosomal trafficking disables regulatory T cells in vasculitis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- PPAR-α Agonist Suppresses Expression of Immune Mediators in B Cells in a Murine Model of Systemic Lupus Erythematosus.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Unlocking the black box: multimodal imaging and quantitative analysis of plant vesicular trafficking.Advanced biotechnology · 2026Review
- Cancer Stem Cells Shift Metabolite Acetyl-Coenzyme A to Abrogate the Differentiation of CD103Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of MicroRNAs in Treg-Derived Extracellular Vesicles: A Narrative Review Focusing on Immune-Related Diseases.Journal of immunology research · 2026Review
- Immune Aging in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- Exosomes as immunomodulators in autoimmune inflammation: implications for primary Sjögren's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- The Role of Notch Signaling and Gut Microbiota in Autoinflammatory Diseases: Mechanisms and Future Views.Biomedicines · 2025Review
- Challenges in Diagnosis and Management of Takayasu Arteritis: A Case Report Highlighting Vascular Complications and Delayed Recognition.Clinical case reports · 2025Article
- Nitric oxide facilitates the S-nitrosylation and deubiquitination of Notch1 protein to maintain cancer stem cells in human NSCLC.Journal of cellular and molecular medicine · 2024Article
- Construction of a prognostic model with exosome biogenesis- and release-related genes and identification of RAB27B in immune infiltration of pancreatic cancer.Translational cancer research · 2024Article
- Vascular disease persistence in giant cell arteritis: are stromal cells neglected?Annals of the rheumatic diseases · 2024Review
- Immune checkpoints in autoimmune vasculitis.Best practice & research. Clinical rheumatology · 2024Review
- The role of transcription factors in the pathogenesis and therapeutic targeting of vascular diseases.Frontiers in cardiovascular medicine · 2024Review
- Exosomes and the cardiovascular system: role in cardiovascular health and disease.The Journal of physiology · 2023Article
- Stem-like CD4Science translational medicine · 2023Article
- JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNAGenes & diseases · 2023Article
- The biogenesis and secretion of exosomes and multivesicular bodies (MVBs): Intercellular shuttles and implications in human diseases.Genes & diseases · 2023Review
- Immune aging - A mechanism in autoimmune disease.Seminars in immunology · 2023Review
- Deficiency of the CD155-CD96 immune checkpoint controls IL-9 production in giant cell arteritis.Cell reports. Medicine · 2023Article
- Immunology of Giant Cell Arteritis.Circulation research · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The aorta and the large conductive arteries are immunoprivileged tissues and are protected against inflammatory attack. A breakdown of immunoprivilege leads to autoimmune vasculitis, such as giant cell arteritis, in which CD8+ Treg cells fail to contain CD4+ T cells and macrophages, resulting in the formation of tissue-destructive granulomatous lesions. Here, we report that the molecular defect of malfunctioning CD8+ Treg cells lies in aberrant NOTCH4 signaling that deviates endosomal trafficking and minimizes exosome production. By transcriptionally controlling the profile of RAB GTPases, NOTCH4 signaling restricted vesicular secretion of the enzyme NADPH oxidase 2 (NOX2). Specifically, NOTCH4hiCD8+ Treg cells increased RAB5A and RAB11A expression and suppressed RAB7A, culminating in the accumulation of early and recycling endosomes and sequestering of NOX2 in an intracellular compartment. RAB7AloCD8+ Treg cells failed in the surface translocation and exosomal release of NOX2. NOTCH4hiRAB5AhiRAB7AloRAB11AhiCD8+ Treg cells left adaptive immunity unopposed, enabling a breakdown in tissue tolerance and aggressive vessel wall inflammation. Inhibiting NOTCH4 signaling corrected the defect and protected arteries from inflammatory insult. This study implicates NOTCH4-dependent transcriptional control of RAB proteins and intracellular vesicle trafficking in autoimmune disease and in vascular inflammation.
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