ArticleThe Journal of experimental medicine2023
Immune-interacting lymphatic endothelial subtype at capillary terminals drives lymphatic malformation.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Sirolimus treatment for paediatric head and neck lymphatic malformations: a systematic review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023Pooled it
- Medical Therapies for Pediatric Lymphatic Malformations: A Systematic Review.Journal of cutaneous medicine and surgeryPooled it
- Application value of indocyanine green lymphography in the management of stage I/IIA microcystic lymphatic malformation of the tongue.Head & face medicine · 2025Trial
- Cardiac lymphatic dysfunction and repair in cardiovascular disease.Nature reviews. Cardiology · 2026Review
- 3D chromatin organisation contributes to the regulatory logic in differentiating lymphatic endothelium.EMBO reports · 2026Article
- Review
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- RAS-PI3Kα signaling regulates KrasG12D-induced lymphangiogenesis in complex lymphatic anomalies.Disease models & mechanisms · 2026Article
- Blood and lymphatic vascular network in bone injury repair: from molecular mechanisms to therapeutic strategies.Science China. Life sciences · 2026Review
- The crosstalk between lymphatic endothelial cells and immune cells in Physiological and Pathological conditions.Cellular and molecular life sciences : CMLS · 2026Review
- Oncogenic PIK3CA mutations shape an immunoregulatory microenvironment in mosaic overgrowth disorders.PNAS nexus · 2026Article
- Spatially Resolved Heterogeneity of Lymphatic Vasculature in the Adult Lung-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- VEGFR2 is required for VEGF-C-VEGFR3-PI3Kα-mediated sprouting lymphangiogenesis.Nature communications · 2026Article
- VEGF-D-induced intraosseous lymphangiogenesis drives site-specific heterotopic bone resorption.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Identification of synovial lymphatic system in the temporomandibular joint and their roles in arthritis and pain.Nature communications · 2026Article
- IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma.Cancer cell · 2026Article
- Multidimensional single-cell analysis reveals immune dysfunction and inflammatory response in lymphatic malformations.Protein & cell · 2026Article
- Cooperative ETS transcription factors are required for lymphatic endothelial cell integrity and resilience.The Journal of clinical investigation · 2026Article
- Spatial Transcriptomics of TMJ Reveals a Remodeling Fibroblast-Immune Microenvironment Driving Arthritis Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Insights into KIF11 pathogenesis in microcephaly-lymphedema-chorioretinopathy syndrome from a lymphatic perspective.JCI insight · 2026Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Oncogenic mutations in PIK3CA, encoding p110α-PI3K, are a common cause of venous and lymphatic malformations. Vessel type-specific disease pathogenesis is poorly understood, hampering development of efficient therapies. Here, we reveal a new immune-interacting subtype of Ptx3-positive dermal lymphatic capillary endothelial cells (iLECs) that recruit pro-lymphangiogenic macrophages to promote progressive lymphatic overgrowth. Mouse model of Pik3caH1047R-driven vascular malformations showed that proliferation was induced in both venous and lymphatic ECs but sustained selectively in LECs of advanced lesions. Single-cell transcriptomics identified the iLEC population, residing at lymphatic capillary terminals of normal vasculature, that was expanded in Pik3caH1047R mice. Expression of pro-inflammatory genes, including monocyte/macrophage chemokine Ccl2, in Pik3caH1047R-iLECs was associated with recruitment of VEGF-C-producing macrophages. Macrophage depletion, CCL2 blockade, or anti-inflammatory COX-2 inhibition limited Pik3caH1047R-driven lymphangiogenesis. Thus, targeting the paracrine crosstalk involving iLECs and macrophages provides a new therapeutic opportunity for lymphatic malformations. Identification of iLECs further indicates that peripheral lymphatic vessels not only respond to but also actively orchestrate inflammatory processes.
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What Socratic holds
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 Socratic graph.