ArticleTransplantation2019
Differential Regulation of T-cell Immunity and Tolerance by Stromal Laminin Expressed in the Lymph Node.
Article in Transplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Lymph node extracellular matrix skews the immune function of human fibroblastic reticular cells.iScience · 2026Article
- HEV-Targeted Antibody-Drug Conjugate Promotes Long-Term Cardiac Allograft Acceptance.Circulation · 2026Article
- Microphysiological Systems of Lymphatics and Immune Organs.Advanced healthcare materials · 2026Review
- Immunosuppressants rewire the gut microbiome-alloimmune axis through time-dependent and tissue-specific mechanisms.Cell communication and signaling : CCS · 2025Article
- Immunosuppressants Rewire the Gut Microbiome-Alloimmune Axis Through Time-Dependent and Tissue-Specific Mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Lymph nodes molecular subtypes unravel lymph nodes heterogeneity and clinical implications in colorectal cancer.Nature communications · 2025Article
- Integrated profiling of metaplastic breast cancer identifies putative master regulators of intratumoral heterogeneity.NPJ breast cancer · 2025Article
- CXCL12+ fibroblastic reticular cells in lymph nodes facilitate immune tolerance by regulating T cell-mediated alloimmunity.The Journal of clinical investigation · 2025Article
- Rapamycin immunomodulation utilizes time-dependent alterations of lymph node architecture, leukocyte trafficking, and gut microbiome.JCI insight · 2025Article
- Skin Deep and Beyond: Unravelling B Cell Extracellular Matrix Interactions in Cutaneous Immunity and Disease.Experimental dermatology · 2025Review
- Review
- Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets.Frontiers in pharmacology · 2024Article
- Mechanisms and therapeutic strategies to combat the recurrence and progression of hepatocellular carcinoma after thermal ablation.Journal of interventional medicine · 2023Article
- Harnessing Biomaterials to Study and Direct Antigen-Specific Immunotherapy.ACS applied bio materials · 2023Review
- The aging of the immune system and its implications for transplantation.GeroScience · 2023Review
- FRC transplantation restores lymph node conduit defects in laminin α4-deficient mice.JCI insight · 2023Article
- Single-cell and spatial transcriptome analyses revealed cell heterogeneity and immune environment alternations in metastatic axillary lymph nodes in breast cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation.Nature communications · 2023Article
- Tissue-Targeted Drug Delivery Strategies to Promote Antigen-Specific Immune Tolerance.Advanced healthcare materials · 2023Review
- Delivery of costimulatory blockade to lymph nodes promotes transplant acceptance in mice.The Journal of clinical investigation · 2022Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundStromal laminins α4 and α5 are differentially regulated in transplant tolerance and immunity, respectively, resulting in altered T-cell trafficking. We hypothesized that laminins directly regulated T-cell activation and polarization.
methodsHuman and mouse CD4 T cells were activated in Th1, Th2, Th17, or regulatory T cell (Treg) environments with/without laminin α4 and/or α5. Laminin α5 receptors were blocked with anti-α6 integrin or anti-α-dystroglycan (αDG) monoclonal antibodies, and T-cell polarization was determined. T-cell receptor transgenic TEa CD4 cells that recognized donor alloantigen were transferred into C57BL/6 mice that received alloantigen or cardiac allografts. Laminin receptors were blocked, and TEa T-cell migration and differentiation were assessed. Laminin expression was measured in several models of immunity and tolerance.
resultsIn diverse models, laminins α4 and α5 were differentially regulated. Immunity was associated with decreased laminin α4:α5 ratio, while tolerance was associated with an increased ratio. Laminin α4 inhibited CD4+ T-cell proliferation and Th1, Th2, and Th17 polarization but favored Treg induction. Laminin α5 favored T-cell activation and Th1, Th2, and Th17 polarization and inhibited Treg. Laminin α5 was recognized by T cell integrin α6 and is important for activation and inhibition of Treg. Laminin α5 was also recognized by T cell α-DG and required for Th17 differentiation. Anti-α6 integrin or anti-DG prolonged allograft survival.
conclusionsLaminins α4 and α5 are coinhibitory and costimulatory ligands for human and mouse CD4 T cells, respectively. Laminins and their receptors modulate immune responses by acting as one of the molecular switches for immunity or suppression.
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