ArticleThe Journal of experimental medicine2007
RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla.
Article in The Journal of experimental medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 247 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
247 citing papers in PubMed, 477 citations in OpenAlex.
- Rank-dependent control of tuft and BEST4 cell development in the intestine.Nature communications · 2026Article
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Article
- RORγtScience immunology · 2026Article
- Human inborn errors of the alternative NF-κB pathway.Journal of human immunity · 2026Review
- Bioelectronic modulation of the thymic "genetic mirror": 448 kHz radiofrequency stimulation as a novel strategy for immune tolerance induction in type 1 diabetes.Frontiers in immunology · 2026Review
- The interaction network between group 3 innate lymphoid cells and other cells.Fundamental research · 2025Review
- Thymic Interferons: A Little Goes a Long Way.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
- Deconstructing the Thymic Microenvironment Through Genesis to Senescence.Immunological reviews · 2025Review
- Thymflammation: The Role of a Constitutively Active Inflammatory Network and "Ectopic" Cell Types in the Thymus in the Induction of T Cell Tolerance and Beyond.Immunological reviews · 2025Review
- Efficacy and immune-related adverse events of pembrolizumab with bone-modifying agents in female patients with breast cancer.The oncologist · 2025Article
- Endogenous thymic regeneration: restoring T cell production following injury.Nature reviews. Immunology · 2025Review
- Thymic Crosstalk: An Overview of the Complex Cellular Interactions that Control the Establishment of T-Cell Tolerance.Advances in experimental medicine and biology · 2025Review
- Antigen presentation for central tolerance induction.Nature reviews. Immunology · 2025Review
- RANK/RANKL Signaling Pathway in Breast Development and Cancer.Advances in experimental medicine and biology · 2025Review
- The Autoimmune Regulator (AIRE) Gene, The Master Activator of Self-Antigen Expression in the Thymus.Advances in experimental medicine and biology · 2025Review
- The Ins and Outs of Thymic Epithelial Cell Differentiation and Function.Advances in experimental medicine and biology · 2025Review
- Article
- Generation and repair of thymic epithelial cells.The Journal of experimental medicine · 2024Review
187 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by expressing tissue-restricted antigens to help purge the emerging T cell receptor repertoire of self-reactive specificities. Here we demonstrate a novel role for a CD4(+)3(-) inducer cell population, previously linked to development of organized secondary lymphoid structures and maintenance of T cell memory in the functional regulation of Aire-mediated promiscuous gene expression in the thymus. CD4(+)3(-) cells are closely associated with mTECs in adult thymus, and in fetal thymus their appearance is temporally linked with the appearance of Aire(+) mTECs. We show that RANKL signals from this cell promote the maturation of RANK-expressing CD80(-)Aire(-) mTEC progenitors into CD80(+)Aire(+) mTECs, and that transplantation of RANK-deficient thymic stroma into immunodeficient hosts induces autoimmunity. Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in intrathymic self-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.