ArticleeLife2023
CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Generation of effector CD4Stem cell reports · 2026Article
- 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
- Aging-Driven Immunosuppression: The Role of Tregs in the Ovarian Tumor Microenvironment.Aging cell · 2026Article
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Unbiased recording and identification of thymic cellular interactomes using synthetic Notch receptors.Nature communications · 2026Article
- The differentiation and function of heterogeneous thymic dendritic cell subsets require signals provided by distinct thymocyte cell types.Nature immunology · 2026Article
- Unexpected heterogeneity and tissue-specific properties of the thymic hematopoietic antigen-presenting cell network.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrin CD103 reveals a distinct developmental pathway of autoreactive thymocytes in TCR transgenic mice.Nature communications · 2025Article
- Intrathymic Regulation of Dendritic Cell Subsets and Their Contributions to Central Tolerance.Immunological reviews · 2025Review
- Antigen presentation for central tolerance induction.Nature reviews. Immunology · 2025Review
- Intrathymic Cell Migration: Implications in Thymocyte Development and T Lymphocyte Repertoire Formation.Advances in experimental medicine and biology · 2025Review
- Article
- Comprehensive Flow Cytometric, Immunohistologic, and Molecular Assessment of Thymus Function in Rhesus Macaques.ImmunoHorizons · 2024Article
- Review
- A spatial human thymus cell atlas mapped to a continuous tissue axis.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Central tolerance ensures autoreactive T cells are eliminated or diverted to the regulatory T cell lineage, thus preventing autoimmunity. To undergo central tolerance, thymocytes must enter the medulla to test their T-cell receptors (TCRs) for autoreactivity against the diverse self-antigens displayed by antigen-presenting cells (APCs). While CCR7 is known to promote thymocyte medullary entry and negative selection, our previous studies implicate CCR4 in these processes, raising the question of whether CCR4 and CCR7 play distinct or redundant roles in central tolerance. Here, synchronized positive selection assays, two-photon time-lapse microscopy, and quantification of TCR-signaled apoptotic thymocytes, demonstrate that CCR4 and CCR7 promote medullary accumulation and central tolerance of distinct post-positive selection thymocyte subsets in mice. CCR4 is upregulated within hours of positive selection signaling and promotes medullary entry and clonal deletion of immature post-positive selection thymocytes. In contrast, CCR7 is expressed several days later and is required for medullary localization and negative selection of mature thymocytes. In addition, CCR4 and CCR7 differentially enforce self-tolerance, with CCR4 enforcing tolerance to self-antigens presented by activated APCs, which express CCR4 ligands. Our findings show that CCR7 expression is not synonymous with medullary localization and support a revised model of central tolerance in which CCR4 and CCR7 promote early and late stages of negative selection, respectively, via interactions with distinct APC subsets.
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