ArticleThe Journal of clinical investigation2025
CXCL12+ fibroblastic reticular cells in lymph nodes facilitate immune tolerance by regulating T cell-mediated alloimmunity.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed.
- Lymph node extracellular matrix skews the immune function of human fibroblastic reticular cells.iScience · 2026Article
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Single-cell RNA sequencing of adenoid cystic carcinoma of the breast reveals cellular heterogeneity and tumor microenvironment features.BMC medical genomics · 2026Article
- Immunometabolic Reprogramming of Fibroblastic Reticular Cells in the Tumor Immune Microenvironment.BioMed research international · 2026Review
- Advances in nanomaterial-based delivery systems for inducing transplantation tolerance.Frontiers in immunology · 2026Review
- Integrative Transcriptomic Analysis Identifies CXCL12 as a Candidate Hub Gene Associated with CD4⁺ T-Cell Immune Network Remodeling in Secondary Lymphedema.Journal of inflammation research · 2026Article
- From stasis to systematics: deciphering the pathophysiology of secondary lymphedema through omics.Frontiers in immunology · 2026Review
- Perivascular Tertiary Lymphoid Structures in Autoimmune Disease.Immunological reviews · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
Fibroblastic reticular cells (FRCs) are the master regulators of the lymph node (LN) microenvironment. However, the role of specific FRC subsets in controlling alloimmune responses remains to be studied. Single-cell RNA sequencing (scRNA-Seq) of naive and draining LNs (DLNs) of heart-transplanted mice and human LNs revealed a specific subset of CXCL12hi FRCs that expressed high levels of lymphotoxin-β receptor (LTβR) and are enriched in the expression of immunoregulatory genes. CXCL12hi FRCs had high expression of CCL19, CCL21, indoleamine 2,3-dioxygenase (IDO), IL-10, and TGF-β1. Adoptive transfer of ex vivo-expanded FRCs resulted in their homing to LNs and induced immunosuppressive environments in DLNs to promote heart allograft acceptance. Genetic deletion of LTβR and Cxcl12 in FRCs increased alloreactivity, abrogating the effect of costimulatory blockade in prolonging heart allograft survival. As compared with WT recipients, CXCL12+ FRC-deficient recipients exhibited increased differentiation of CD4+ T cells into Th1 cells. Nano delivery of CXCL12 to DLNs improved allograft survival in heart-transplanted mice. Our study highlights the importance of DLN CXCL12hi FRCs in promoting transplant tolerance.
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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.