ArticleThe Journal of experimental medicine2015
CCR4 promotes medullary entry and thymocyte-dendritic cell interactions required for central tolerance.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The trial behind it
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
54 citing papers in PubMed, 84 citations in OpenAlex.
- Type 2 conventional dendritic cells and regulatory T cells form a barrier tissue circuit to control allergic inflammation.bioRxiv : the preprint server for biology · 2026Article
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Unraveling CD8 lineage decisions reveals that functionally distinct CD8Nature immunology · 2026Article
- Claudin 1-mediated positioning of DC1 to mTECs is essential for maintenance of central tolerance.The Journal of experimental medicine · 2026Article
- Intrathymic Regulation of Dendritic Cell Subsets and Their Contributions to Central Tolerance.Immunological reviews · 2025Review
- Basic interactions responsible for thymus function explain the convoluted medulla shape.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Developmental features and unique characteristics of peptide-specific PLZFNature communications · 2025Article
- Double-Negative CD4 CD8 Absolute Count Plays a Mediating Role in the Causal Relationship Between Plasma Lipids and Parkinson's Disease: A Mendel Randomized Study.Molecular neurobiology · 2025Article
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Intrathymic Cell Migration: Implications in Thymocyte Development and T Lymphocyte Repertoire Formation.Advances in experimental medicine and biology · 2025Review
- Article
- Regulation of Tumor Dendritic Cells by Programmed Cell Death 1 Pathways.Journal of immunology (Baltimore, Md. : 1950) · 2024Review
- Navigating the thymic landscape through development: from cellular atlas to tissue cartography.Genes and immunity · 2024Article
- A guide to thymic selection of T cells.Nature reviews. Immunology · 2024Review
- Review
- CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.eLife · 2023Article
- Studying T Cell Development in Neonatal and Adult Thymic Slices.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Type 2 cytokines in the thymus activate SirpαNature immunology · 2022Article
- Central tolerance is impaired in the middle-aged thymic environment.Aging cell · 2022Article
- Thymocytes trigger self-antigen-controlling pathways in immature medullary thymic epithelial stages.eLife · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Autoimmunity results from a breakdown in central or peripheral tolerance. To establish central tolerance, developing T cells must enter the thymic medulla, where they scan antigen-presenting cells (APCs) displaying a diverse array of autoantigens. If a thymocyte is activated by a self-antigen, the cell undergoes either deletion or diversion into the regulatory T cell (T reg) lineage, thus maintaining self-tolerance. Mechanisms promoting thymocyte medullary entry and interactions with APCs are incompletely understood. CCR4 is poised to contribute to central tolerance due to its expression by post-positive selection thymocytes, and expression of its ligands by medullary thymic dendritic cells (DCs). Here, we use two-photon time-lapse microscopy to demonstrate that CCR4 promotes medullary entry of the earliest post-positive selection thymocytes, as well as efficient interactions between medullary thymocytes and DCs. In keeping with the contribution of thymic DCs to central tolerance, CCR4 is involved in regulating negative selection of polyclonal and T cell receptor (TCR) transgenic thymocytes. In the absence of CCR4, autoreactive T cells accumulate in secondary lymphoid organs and autoimmunity ensues. These studies reveal a previously unappreciated role for CCR4 in the establishment 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.