ArticleNature communications2022
Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Prognostic and clinicopathological significance of tertiary lymphoid structure in non-small cell lung cancer: a systematic review and meta-analysis.BMC cancer · 2024Pooled it
- Associations between tertiary lymphoid structure density and immune checkpoint inhibitor efficacy in solid tumors: systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Tertiary lymphoid structures in gastrointestinal cancer: orchestrating tumour microenvironmental immune subcycles to elegantly amplify the cancer immunity cycle.Annals of medicine · 2026Review
- Tertiary lymphoid structures in cancer: their development, composition, clinical prognosis, and the drivers of the anti-tumor responses.Molecular biomedicine · 2026Review
- Tertiary lymphoid structures in neuroinflammation coordinate neuroimmune homeostasis and pathological progression.Journal of neuroinflammation · 2026Review
- Anti-angiogenic therapy combined with immune checkpoint blockade mediates CCR7 + CD8 + T-cell entry into HCC through high endothelial venules.Hepatology (Baltimore, Md.) · 2026Article
- Tertiary Lymphoid Structure: A Potential Therapeutic Target Affecting Immune Response in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2026Review
- Prognostic value of tertiary lymphoid structures in locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoimmunotherapy: a retrospective study.Journal of cardiothoracic surgery · 2026Article
- Spatial characterization of skin lesions in discoid and systemic lupus erythematosus.Nature communications · 2026Article
- The CXCL13 hub in obesity-related metabolic inflammation: regulation of spatiotemporal heterogeneity and targeted strategies.The Journal of endocrinology · 2026Review
- Tertiary lymphoid structure topotypes in intrahepatic cholangiocarcinoma: spatial immunity, checkpoint-response associations, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Spatial niche remodeling of senescent liver-resident immune cells and its role in chronic liver diseases.Frontiers in medicine · 2026Review
- The role of notch signaling in tumor angiogenesis in hematological malignancies.Frontiers in oncology · 2026Review
- High Phosphate Load Induces De Novo Formation of Tertiary Lymphoid Structures in the Kidney.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Tertiary lymphoid structures in cancer: spatiotemporal heterogeneity, immune orchestration, and translational opportunities.Journal of hematology & oncology · 2025Review
- The roles of tertiary lymphoid structures in orchestrating immune responses in peripheral organs.Inflammation and regeneration · 2025Review
- Dynamic remodeling of tertiary lymphoid structures in response to cancer therapy: a recent review.Cancer immunology, immunotherapy : CII · 2025Review
- Organ-specific features of human kidney lymphatics are disrupted in chronic transplant rejection.The Journal of clinical investigation · 2025Article
- Perivascular Tertiary Lymphoid Structures in Autoimmune Disease.Immunological reviews · 2025Review
- Current research of the Notch pathway in hepatocellular carcinoma.European journal of medical research · 2025Review
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tertiary lymphoid structures (TLS) are lymph node-like immune cell clusters that emerge during chronic inflammation in non-lymphoid organs like the kidney, but their origin remains not well understood. Here we show, using conditional deletion strategies of the canonical Notch signaling mediator Rbpj, that loss of endothelial Notch signaling in adult mice induces the spontaneous formation of bona fide TLS in the kidney, liver and lung, based on molecular, cellular and structural criteria. These TLS form in a stereotypical manner around parenchymal arteries, while secondary lymphoid structures remained largely unchanged. This effect is mediated by endothelium of blood vessels, but not lymphatics, since a lymphatic endothelial-specific targeting strategy did not result in TLS formation, and involves loss of arterial specification and concomitant acquisition of a high endothelial cell phenotype, as shown by transcriptional analysis of kidney endothelial cells. This indicates a so far unrecognized role for vascular endothelial cells and Notch signaling in TLS initiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.