ArticleJournal of immunology (Baltimore, Md. : 1950)2010
Lymphotoxin signals from positively selected thymocytes regulate the terminal differentiation of medullary thymic epithelial cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 137 citations in OpenAlex.
- Epithelial chemokine CCL25 integrates T cell development and intestinal homeostasis.The Journal of experimental medicine · 2026Article
- Morphometric analysis of the thymic epithelial cell network using integrated and orthogonal digital pathology approaches.Communications biology · 2026Article
- An iPSC-based in vitro model recapitulates human thymic epithelial development and multi-lineage specification.Nature communications · 2025Article
- Deconstructing the Thymic Microenvironment Through Genesis to Senescence.Immunological reviews · 2025Review
- It's Time to Unite: Diversity and Coordination of Thymic Stromal Cells for T Cell Selection and Organ Integrity.Immunological reviews · 2025Review
- Generation and repair of thymic epithelial cells.The Journal of experimental medicine · 2024Review
- Assembling the thymus medulla: Development and function of epithelial cell heterogeneity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- Direct and indirect RANK and CD40 signaling regulate the maintenance of thymic epithelial cell frequency and properties in the adult thymus.Frontiers in immunology · 2024Article
- Revisiting Aire and tissue-restricted antigens at single-cell resolution.Frontiers in immunology · 2023Review
- Diversity in Cortical Thymic Epithelial Cells Occurs through Loss of a Foxn1-Dependent Gene Signature Driven by Stage-Specific Thymocyte Cross-Talk.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Mesenchymal stromal cells in the thymus.Inflammation and regeneration · 2022Review
- Article
- Fine-tuning of β-catenin in mouse thymic epithelial cells is required for postnatal T-cell development.eLife · 2022Article
- The transcription factor Sox4 is required for thymic tuft cell development.International immunology · 2022Article
- Thymus Functionality Needs More Than a Few TECs.Frontiers in immunology · 2022Review
- Signaling Crosstalks Drive Generation and Regeneration of the Thymus.Frontiers in immunology · 2022Review
- Cytosolic Nuclear Sensor Dhx9 Controls Medullary Thymic Epithelial Cell Differentiation by p53-Mediated Pathways.Frontiers in immunology · 2022Article
- Epigenetic modifications in thymic epithelial cells: an evolutionary perspective for thymus atrophy.Clinical epigenetics · 2021Review
- Lymphotoxin: from the physiology to the regeneration of the thymic function.Cell death and differentiation · 2021Review
- Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla.Nature communications · 2021Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
The thymic medulla represents a key site for the induction of T cell tolerance. In particular, autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) provide a spectrum of tissue-restricted Ags that, through both direct presentation and cross-presentation by dendritic cells, purge the developing T cell repertoire of autoimmune specificities. Despite this role, the mechanisms of Aire(+) mTEC development remain unclear, particularly those stages that occur post-Aire expression and represent mTEC terminal differentiation. In this study, in mouse thymus, we analyze late-stage mTEC development in relation to the timing and requirements for Aire and involucrin expression, the latter a marker of terminally differentiated epithelium including Hassall's corpuscles. We show that Aire expression and terminal differentiation within the mTEC lineage are temporally separable events that are controlled by distinct mechanisms. We find that whereas mature thymocytes are not essential for Aire(+) mTEC development, use of an inducible ZAP70 transgenic mouse line--in which positive selection can be temporally controlled--demonstrates that the emergence of involucrin(+) mTECs critically depends upon the presence of mature single positive thymocytes. Finally, although initial formation of Aire(+) mTECs depends upon RANK signaling, continued mTEC development to the involucrin(+) stage maps to activation of the LTα-LTβR axis by mature thymocytes. Collectively, our results reveal further complexity in the mechanisms regulating thymus medulla development and highlight the role of distinct TNFRs in initial and terminal differentiation stages in mTECs.
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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.