ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Differential requirement for CCR4 and CCR7 during the development of innate and adaptive αβT cells in the adult thymus.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 70 citations in OpenAlex.
- 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
- 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
- Intrathymic Cell Migration: Implications in Thymocyte Development and T Lymphocyte Repertoire Formation.Advances in experimental medicine and biology · 2025Review
- Assembling the thymus medulla: Development and function of epithelial cell heterogeneity.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.eLife · 2023Article
- Antigen-presenting T cells provide critical B7 co-stimulation for thymic iNKT cell development via CD28-dependent trogocytosis.Cell reports · 2022Article
- Type 2 cytokines in the thymus activate SirpαNature immunology · 2022Article
- Central tolerance is impaired in the middle-aged thymic environment.Aging cell · 2022Article
- CCR4 and CCR5 Involvement in Monocyte-Derived Macrophage Migration in Neuroinflammation.Frontiers in immunology · 2022Article
- How Thymocyte Deletion in the Cortex May Curtail Antigen-Specific T-Regulatory Cell Development in the Medulla.Frontiers in immunology · 2022Article
- CCR4 is a prognostic biomarker and correlated with immune infiltrates in head and neck squamous cell carcinoma.Annals of translational medicine · 2021Article
- Transcriptional and functional characterization of neonatal circulating Innate Lymphoid Cells.Stem cells translational medicine · 2021Article
- SRSF1 serves as a critical posttranscriptional regulator at the late stage of thymocyte development.Science advances · 2021Article
- Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge.Nature reviews. Immunology · 2020Review
- Article
- From stem cell to immune effector: how adhesion, migration, and polarity shape T-cell and natural killer cell lymphocyte development in vitro and in vivo.Molecular biology of the cell · 2020Review
- A divergent transcriptional landscape underpins the development and functional branching of MAIT cells.Science immunology · 2019Article
- Measuring Thymic Clonal Deletion at the Population Level.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Guidance factors orchestrating regulatory T cell positioning in tissues during development, homeostasis, and response.Immunological reviews · 2019Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
αβT cell development depends upon serial migration of thymocyte precursors through cortical and medullary microenvironments, enabling specialized stromal cells to provide important signals at specific stages of their development. Although conventional αβT cells are subject to clonal deletion in the medulla, entry into the thymus medulla also fosters αβT cell differentiation. For example, during postnatal periods, the medulla is involved in the intrathymic generation of multiple αβT cell lineages, notably the induction of Foxp3(+) regulatory T cell development and the completion of invariant NKT cell development. Although migration of conventional αβT cells to the medulla is mediated by the chemokine receptor CCR7, how other T cell subsets gain access to medullary areas during their normal development is not clear. In this study, we show that combining a panel of thymocyte maturation markers with cell surface analysis of CCR7 and CCR4 identifies distinct stages in the development of multiple αβT cell lineages in the thymus. Although Aire regulates expression of the CCR4 ligands CCL17 and CCL22, we show that CCR4 is dispensable for thymocyte migration and development in the adult thymus, demonstrating defective T cell development in Aire(-/-) mice is not because of a loss of CCR4-mediated migration. Moreover, we reveal that CCR7 controls the development of invariant NKT cells by enabling their access to IL-15 trans-presentation in the thymic medulla and influences the balance of early and late intrathymic stages of Foxp3(+) regulatory T cell development. Collectively, our data identify novel roles for CCR7 during intrathymic T cell development, highlighting its importance in enabling multiple αβT cell lineages to access the thymic medulla.
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