ArticleDiabetologia2019
Phenotypic alterations in pancreatic lymph node stromal cells from human donors with type 1 diabetes and NOD mice.
Article in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- LN-Derived Fibroblastic Reticular Cells and Their Impact on T Cell Response-A Systematic Review.Cells · 2021Pooled it
- Spatial transcriptomics from pancreas and local draining lymph node tissue reveals a lymphotoxin-β signature in human type 1 diabetes.Cell reports · 2026Article
- Intermittent fasting inhibits ferroptosis by modulating CD36 and its palmitoylation to alleviate diabetic dry eye.Cellular & molecular biology letters · 2026Article
- Lymph nodes as gatekeepers of autoimmune diseases.RMD open · 2024Review
- Pancreatic draining lymph nodes (PLNs) serve as a pathogenic hub contributing to the development of type 1 diabetes.Cell & bioscience · 2023Review
- Nanoparticles for Inducing Antigen-Specific T Cell Tolerance in Autoimmune Diseases.Frontiers in immunology · 2022Review
- Altered Frequency and Phenotype of HLA-G-Expressing DC-10 in Type 1 Diabetes Patients at Onset and in Subjects at Risk to Develop the Disease.Frontiers in immunology · 2021Article
- Lymph Node Stromal Cells: Mapmakers of T Cell Immunity.International journal of molecular sciences · 2020Review
- Tissue-Engineered Stromal Reticula to Study Lymph Node Fibroblastic Reticular Cells in Type I Diabetes.Cellular and molecular bioengineering · 2020Article
- Human Lymph Node Stromal Cells Have the Machinery to Regulate Peripheral Tolerance during Health and Rheumatoid Arthritis.International journal of molecular sciences · 2020Article
- Nanoparticles versus Dendritic Cells as Vehicles to Deliver mRNA Encoding Multiple Epitopes for Immunotherapy.Molecular therapy. Methods & clinical development · 2020Article
- Phenotypic alterations in pancreatic lymph node stromal cells from human donors with type 1 diabetes and NOD mice.Diabetologia · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisTolerance induction in lymph nodes can be mediated by both haematopoietic cells (e.g. specific dendritic cells subsets) and by non-haematopoietic cells (e.g. lymph node stromal cells [LNSCs]) when they present peripheral tissue antigens to autoreactive T cells. LNSCs normally regulate T cell trafficking and survival and help to maintain peripheral tolerance by exerting immunosuppressive effects. However, whether autoimmunity can be associated with defective tolerogenic functions of LNSCs is unknown and studies aimed at characterising LNSCs in humans are lacking. We hypothesised that dysregulated T cell responses in pancreatic lymph nodes (PLNs) from donors with type 1 diabetes and from NOD mice may be associated with altered LNSC function.
methodsWe analysed PLNs from donors with type 1 diabetes and NOD mice for LNSC distribution and phenotype using flow cytometry. We assessed the expression of tolerance-related genes in different subsets of LNSCs from human donors, as well as in a population of dendritic cells enriched in autoimmune regulator (AIRE)
resultsThe relative frequency of different LNSC subsets was altered in both donors with type 1 diabetes and NOD mice, and both MHC class II and programmed death-ligand 1 (PD-L1) expression were upregulated in human type 1 diabetes. Tolerance-related genes showed similar expression profiles between mouse and human LNSCs at steady state but were generally upregulated in the context of human type 1 diabetes, while, at the same time, many such genes were downregulated in the AIRE-enriched dendritic cell population. CONCLUSION/
interpretationOur study shows that LNSCs are substantially altered in type 1 diabetes, but, surprisingly, they exhibit an enhanced tolerogenic phenotype along with increased antigen-presenting potential, which may indicate an attempt to offset dendritic cell-related tolerogenic defects in tolerance. Thus, LNSCs could constitute alternative therapeutic targets in which to deliver antigens to help re-establish tolerance and prevent or treat type 1 diabetes. DATA AVAILABILITY: All data generated or analysed during this study are included in the published article (and its online supplementary files). Biomark gene expression data were deposited on the Mendeley repository at https://data.mendeley.com/datasets/d9rdzdmvyf/1 . Any other raw datasets are available from the corresponding author on reasonable request. No applicable resources were generated or analysed during the current study.
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