ArticleThe Journal of clinical investigation2022
Lymph node fibroblastic reticular cells preserve a tolerogenic niche in allograft transplantation through laminin α4.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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Who cites it
31 citing papers in PubMed, 32 citations in OpenAlex.
- Lymph node extracellular matrix skews the immune function of human fibroblastic reticular cells.iScience · 2026Article
- Integrin α7-Driven Senescence-Associated Follicular Helper T Cell Adhesion Induces Tertiary Lymphoid Structures in Nishiura Mice.International journal of molecular sciences · 2026Article
- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- HEV-Targeted Antibody-Drug Conjugate Promotes Long-Term Cardiac Allograft Acceptance.Circulation · 2026Article
- Dissecting origin factors of lymph node metastasis in non-small cell lung cancer via multimodal omics.Nature communications · 2026Article
- Bioinformatics and machine learning-driven discovery of candidate tissue diagnostic markers for endometriosis with experimental verification.Frontiers in endocrinology · 2026Article
- Phenotypic alterations in the immune system and tolerance induction in tumor-draining lymph nodes.Iranian journal of basic medical sciences · 2026Review
- Fibroblastic FLT3L supports lymph node dendritic cells in the interfollicular niche.Nature immunology · 2025Article
- Immunosuppressants rewire the gut microbiome-alloimmune axis through time-dependent and tissue-specific mechanisms.Cell communication and signaling : CCS · 2025Article
- Urinary endotrophin as a biomarker for T cell-mediated rejection-associated fibrogenesis in kidney transplant recipients.Clinical kidney journal · 2025Article
- Immunosuppressants Rewire the Gut Microbiome-Alloimmune Axis Through Time-Dependent and Tissue-Specific Mechanisms.bioRxiv : the preprint server for biology · 2025Article
- CXCL12+ fibroblastic reticular cells in lymph nodes facilitate immune tolerance by regulating T cell-mediated alloimmunity.The Journal of clinical investigation · 2025Article
- LAMA4Cell communication and signaling : CCS · 2025Article
- Rapamycin immunomodulation utilizes time-dependent alterations of lymph node architecture, leukocyte trafficking, and gut microbiome.JCI insight · 2025Article
- Lymphatic messengers: Non-antigen soluble mediators from diseased tissues to draining lymph nodes.Current opinion in immunology · 2025Review
- Review
- Nerves, nodes, and neoplasia.Frontiers in immunology · 2025Review
- Extracellular matrix-related genes-based prognostic signature for cervical cancer: association of LAMA4 expression with prognosis and response to immunotherapy.Frontiers in oncology · 2025Article
- Protective fibroblastic niches in secondary lymphoid organs.The Journal of experimental medicine · 2024Review
- Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
Lymph node (LN) fibroblastic reticular cells (FRCs) define LN niches and regulate lymphocyte homeostasis through producing diverse extracellular matrix (ECM) components. We examined the role of ECM laminin α4 (Lama4) using FRC-Lama4 conditional KO Pdgfrb-Cre-/- × Lama4fl/fl mice. Single-cell RNA-sequencing (scRNA-Seq) data showed the promoter gene Pdgfrb was exclusively expressed in FRCs. Depleting FRC-Lama4 reduced Tregs and dendritic cells, decreased high endothelial venules, impaired the conduit system, and downregulated T cell survival factors in LNs. FRC-Lama4 depletion impaired the homing of lymphocytes to LNs in homeostasis and after allografting. Alloantigen-specific T cells proliferated, were activated to greater degrees in LNs lacking FRC-Lama4, and were more prone to differentiate into effector phenotypes relative to the Treg phenotype. In murine cardiac transplantation, tolerogenic immunosuppression was not effective in FRC-Lama4 recipients, which produced more alloantibodies than WT. After lung transplantation, FRC-Lama4-KO mice had more severe graft rejection with fewer Tregs in their LNs. Overall, FRC-Lama4 critically contributes to a tolerogenic LN niche by supporting T cell migration, constraining T cell activation and proliferation, and promoting Treg differentiation. Hence, it serves as a therapeutic target for immunoengineering.
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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.