ArticleJournal of immunology (Baltimore, Md. : 1950)2008
The lymphotoxin pathway regulates Aire-independent expression of ectopic genes and chemokines in thymic stromal cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 103 citations in OpenAlex.
- Spatial transcriptomics reveals molecular heterogeneity and subtype-specific therapeutic targets in small cell lung cancer.NPJ precision oncology · 2026Article
- Neural Crest-Derived Mesenchymal Cells Support Thymic Reconstitution After Lethal Irradiation.European journal of immunology · 2025Article
- Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance.Cell reports · 2024Article
- Systematic analysis of the prognostic value and immunological function of LTBR in human cancer.Aging · 2024Article
- The thymoproteasome in shaping the CD8Current opinion in immunology · 2023Review
- CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.eLife · 2023Article
- Age-Associated Changes to Lymph Node Fibroblastic Reticular Cells.Frontiers in aging · 2022Article
- Lymphotoxin: from the physiology to the regeneration of the thymic function.Cell death and differentiation · 2021Review
- The fibroblast: An emerging key player in thymic T cell selection.Immunological reviews · 2021Review
- Review
- Medullary stromal cells synergize their production and capture of CCL21 for T-cell emigration from neonatal mouse thymus.Blood advances · 2021Article
- The Multifaceted Roles of B Cells in the Thymus: From Immune Tolerance to Autoimmunity.Frontiers in immunology · 2021Review
- Article
- Fibroblasts as a source of self-antigens for central immune tolerance.Nature immunology · 2020Article
- Non-Epithelial Thymic Stromal Cells: Unsung Heroes in Thymus Organogenesis and T Cell Development.Frontiers in immunology · 2020Review
- Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration.Frontiers in immunology · 2019Article
- Endothelial cells act as gatekeepers for LTβR-dependent thymocyte emigration.The Journal of experimental medicine · 2018Article
- T-cell egress from the thymus: Should I stay or should I go?Journal of leukocyte biology · 2018Review
- Nuclear Factor-kappaB in Autoimmunity: Man and Mouse.Frontiers in immunology · 2018Review
- Twenty Years of AIRE.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Medullary thymic epithelial cells (mTEC) play an important and unique role in central tolerance, expressing tissue-restricted Ags (TRA) which delete thymocytes autoreactive to peripheral organs. Since deficiencies in this cell type or activity can lead to devastating autoimmune diseases, it is important to understand the factors which regulate mTEC differentiation and function. Lymphotoxin (LT) ligands and the LTbetaR have been recently shown to be important regulators of mTEC biology; however, the precise role of this pathway in the thymus is not clear. In this study, we have investigated the impact of this signaling pathway in greater detail, focusing not only on mTEC but also on other thymic stromal cell subsets. LTbetaR expression was found in all TEC subsets, but the highest levels were detected in MTS-15(+) thymic fibroblasts. Rather than directing the expression of the autoimmune regulator Aire in mTEC, we found LTbetaR signals were important for TRA expression in a distinct population of mTEC characterized by low levels of MHC class II (mTEC(low)), as well as maintenance of MTS-15(+) fibroblasts. In addition, thymic stromal cell subsets from LT-deficient mice exhibit defects in chemokine production similar to that found in peripheral lymphoid organs of Lta(-/-) and Ltbr(-/-) mice. Thus, we propose a broader role for LTalpha1beta2-LTbetaR signaling in the maintenance of the thymic microenvironments, specifically by regulating TRA and chemokine expression in mTEC(low) for efficient induction of central 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.