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Updated: Jan 13, 2026

Preparation and Applications of Organotypic Thymic Slice Cultures
Published on: August 6, 2016
The differentiation and function of heterogeneous thymic dendritic cell subsets require signals provided by distinct
Jayashree Srinivasan1, Colin R Moore1, Aparna Calindi1
1Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
None:
Dendritic cells are essential for establishing thymic central tolerance; however, mechanisms supporting their homeostasis and activation remain unresolved. Through single-cell transcriptomics and functional assays, we identify seven thymic conventional dendritic cell (cDC) subsets and discriminate their abilities to present self-antigens and induce regulatory T cells. Mice blocked at different stages of T cell development revealed that CD4+ single-positive (CD4SP) and CD8SP thymocytes differentially support homeostasis and activation of type 1 cDCs (cDC1s) versus cDC2s/plasmacytoid DCs (pDCs), respectively. CD8SP thymocytes indirectly support pDC survival and cDC2 thymic migration, and they induce interferon signaling in cDCs, partly by promoting type 3 interferon expression by medullary thymic epithelial cells. By contrast, CD4SP thymocytes undergo cognate interactions with cDCs, inducing CD40 signaling required for activation of cDC1s. Activated cDC1s make nonredundant contributions to central tolerance. Together, this study comprehensively identifies distinct thymic DC subsets and elucidates requirements for cross-talk with thymocyte subsets that support their homeostasis, activation and function.
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