ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2012
Lymphotoxin-beta receptor blockade induces inflammation and fibrosis in tolerized cardiac allografts.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- From mechanisms to therapy: the role of tertiary lymphoid structures in bladder cancer.World journal of surgical oncology · 2026Review
- Regulatory T cell and endothelial cell crosstalk.Nature reviews. Immunology · 2025Review
- Proteomics of Urinary Extracellular Vesicles Highlight the Involvement of Vitronectin and the Fibrinolytic and TNF Pathways as Mechanisms Underlying Renal Fibrosis in Kidney Transplant Patients.Journal of extracellular biology · 2025Article
- The aging of the immune system and its implications for transplantation.GeroScience · 2023Review
- PD-1/PD-L1 axis in organ fibrosis.Frontiers in immunology · 2023Review
- Review
- The lymph node stromal laminin α5 shapes alloimmunity.The Journal of clinical investigation · 2020Article
- Role of lymph node stroma and microenvironment in T cell tolerance.Immunological reviews · 2019Review
- Gut microbiota-dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes.JCI insight · 2018Article
- Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing.JCI insight · 2018Article
- Lymphotoxin expression in human and murine renal allografts.PloS one · 2018Article
- Interleukin-10 From Marginal Zone Precursor B-Cell Subset Is Required for Costimulatory Blockade-Induced Transplantation Tolerance.Transplantation · 2015Article
- Murine Fibroblastic Reticular Cells From Lymph Node Interact With CD4+ T Cells Through CD40-CD40L.Transplantation · 2015Article
- Lymph Node Stromal Fiber ER-TR7 Modulates CD4+ T Cell Lymph Node Trafficking and Transplant Tolerance.Transplantation · 2015Article
- Vascular endothelial growth factor c/vascular endothelial growth factor receptor 3 signaling regulates chemokine gradients and lymphocyte migration from tissues to lymphatics.Transplantation · 2015Article
- Laminins affect T cell trafficking and allograft fate.The Journal of clinical investigation · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The lymphotoxin system (LT) regulates interactions between lymphocytes and stromal cells to maintain lymphoid microenvironmental homeostasis. Soluble LT beta-receptor-Ig (LTβRIg) blocks lymphocyte LTα1β2-stromal cell LTβR signaling. In a murine cardiac allograft model, LTbRIg treatment reversed the tolerance induced by anti-CD40L antibody leading to graft inflammation and fibrosis. LTβRIg treatment decreased PD-L1 expression by blood endothelial cells, and decreased VCAM-1 while increasing CXCL1, CXCL2, CXCL12, CCL5, CCL21 and IL-6 expression in fibroblastic reticular cells. In secondary lymphoid organs these effects caused T- and B cell zone disruption, loss of CD35(+) follicular dendritic cells and abnormal recruitment of CD11b(+) Ly6G(+) neutrophils. These disruptions correlated with increased numbers of CD8(+) T cells and CD11b(+) Ly6G(+) neutrophils, and decreased numbers of CD4(+) T cells and Foxp3(+) regulatory T cells in the grafts. Depleting neutrophils or blocking neutrophil-attracting chemokines restored normal histology in lymph node, spleen and grafts. Taken together, LTβRIg treatment altered stromal subset, particularly fibroblastic reticular cell, production of cytokines and chemokines, resulting in changes in neutrophil recruitment in spleen, lymph node and grafts, and inflammation and fibrosis associated with decreased Foxp3(+) regulatory T cells and increased CD8(+) T cell infiltration of grafts.
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