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Updated: Jun 27, 2026
Preparation of Single-Cell Suspension of Mouse Thymic Epithelial Cells and Staining of Intracellular Molecules for Flow Cytometric Analysis
Published on: July 26, 2024
Cutting edge: thymic crosstalk regulates delta-like 4 expression on cortical epithelial cells
Emma Fiorini1, Isabel Ferrero, Estelle Merck
1Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Insights
Notch1 receptor and Delta-like 4 (DL4) interactions are crucial for T cell development. DL4 levels on thymic epithelial cells decrease with age, regulated by thymus crosstalk and thymocyte maturation.
Area of Science:
- Immunology
- Developmental Biology
- Cell Biology
Background:
- Notch1 receptor and Delta-like 4 (DL4) ligand interactions are vital for T cell development in the thymus.
- Cortical thymic epithelial cells (cTEC) express DL4, influencing lymphoid progenitors.
Purpose of the Study:
- To investigate the regulation of DL4 expression on cTEC during T cell development.
- To elucidate the role of thymus crosstalk in controlling DL4 levels.
Main Methods:
- Utilized a novel monoclonal antibody (mAb) against DL4.
- Analyzed DL4 expression in fetal, neonatal, and adult wild-type mice.
- Studied mutant mouse strains with blocked thymocyte development.
- Performed reconstitution experiments in mutant mice.
Main Results:
- DL4 levels on cTEC are high in fetal/neonatal thymus and decrease in adults.
- Lymphostromal interactions (thymus crosstalk) are necessary for DL4 down-regulation.
- Thymocyte maturation to CD4(+)CD8(+) and expansion promote DL4 down-regulation.
Conclusions:
- Thymic crosstalk quantitatively regulates Notch1-dependent thymopoiesis.
- DL4 expression on cTEC is a key control point for T cell development rate.
Abstract:
Interactions between Notch1 receptors on lymphoid progenitors and Delta-like 4 (DL4) ligands on cortical thymic epithelial cells (cTEC) are essential for T cell lineage commitment, expansion, and maturation in the thymus. Using a novel mAb against DL4, we show that DL4 levels on cTEC are very high in the fetal and neonatal thymus when thymocyte expansion is maximal but decrease dramatically in the adult when steady-state homeostasis is attained. Analysis of mutant mouse strains where thymocyte development is blocked at different stages indicates that lymphostromal interactions ("thymus crosstalk") are required for DL4 down-regulation on cTEC. Reconstitution of thymocyte development in these mutant mice further suggests that maturation of thymocytes to the CD4(+)CD8(+) stage and concomitant expansion are needed to promote DL4 down-regulation on cTEC. Collectively, our data support a model where thymic crosstalk quantitatively regulates the rate of Notch1-dependent thymopoiesis by controlling DL4 expression levels on cTEC.
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