ArticleProceedings of the National Academy of Sciences of the United States of America2019
Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 2 of them syntheses that pooled it.
What it found
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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.
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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.
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Who cites it
133 citing papers in PubMed, 2 syntheses or guidelines pooled it, 189 citations in OpenAlex.
- Composition and regulation of the immune microenvironment of salivary gland in Sjögren's syndrome.Frontiers in immunology · 2022Pooled it
- Cell and tissue engineering in lymph nodes for cancer immunotherapy.Advanced drug delivery reviews · 2020Pooled it
- Tertiary lymphoid structures in gastrointestinal cancer: orchestrating tumour microenvironmental immune subcycles to elegantly amplify the cancer immunity cycle.Annals of medicine · 2026Review
- Immune cell-derived membrane nanovesicles: A promethean fire for autoimmune disease therapy through immune cell mimicry.Bioactive materials · 2026Review
- Immunogenic cell death and tertiary lymphoid structures: bridging tumour cell death and immune organization.Nature reviews. Immunology · 2026Review
- Review
- From Molecular Pathophysiology to Clinical Trial Design in Sjögren's Disease: A Three-Axis Framework.International journal of molecular sciences · 2026Review
- Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.Journal of hematology & oncology · 2026Review
- Fibroblasts as regulators of lung immunity, repair and fibrosis.Nature reviews. Immunology · 2026Review
- The formation and function of tertiary lymphoid structures.Biomarker research · 2026Review
- A CD4Nature communications · 2026Article
- A Mouthful of Genomic Data: Single-Cell Insights into Salivary Gland Biology and Disease.Biology · 2026Review
- The CXCL13 hub in obesity-related metabolic inflammation: regulation of spatiotemporal heterogeneity and targeted strategies.The Journal of endocrinology · 2026Review
- Single-cell and spatial profiling highlights TB-induced myofibroblasts as drivers of lung pathology.The Journal of experimental medicine · 2026Article
- Multi-modal skin atlas identifies a multicellular immune-stromal community associated with disrupted cornification and specific T cell expansion in atopic dermatitis.Nature communications · 2026Article
- Engineering Adaptive Immunity in 3D: A Patient-Specific Lymphoid Model Using Stromal Networks and Peripheral Blood Mononuclear Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The life cycle of tertiary lymphoid structures in pancreatic cancer-a window of opportunity for immunotherapy.Frontiers in immunology · 2026Review
- Clinical impact and therapeutic potential of tertiary lymphoid structures in melanoma.Frontiers in immunology · 2026Review
- Mechanistic roles and clinical applications of tertiary lymphoid structures in colorectal cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- From TLS architecture to functional immune niches: division of labor among CAFs, HEVs, and antigen-presenting cells in cancer immunotherapy.Frontiers in immunology · 2026Review
73 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.
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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.