ArticleNature immunology2023
Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF.
Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Inherited human TFIIIA deficiency disrupts T cell development.medRxiv : the preprint server for health sciences · 2026Article
- Age- and tissue-dependent diversity of human plasmacytoid dendritic cells uncovers a cycling subset dominant in early life and cancer.Immunity · 2026Article
- T cell development from expanded hematopoietic progenitors reveals initiation control byScience immunology · 2026Article
- Combinatory differentiation of human induced pluripotent stem cells generates functional thymic epithelium driving dendritic cell and CD4/CD8 T cell development.Nature communications · 2026Article
- Upregulation of CD90 correlates with T lineage commitment at the DN2a stage of T cell development.Frontiers in immunology · 2026Article
- The dual nature of TFEBS letters · 2025Review
- Sex-biased human thymic architecture guides T cell development through spatially defined niches.Developmental cell · 2025Article
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- Rediscovering the human thymus through cutting-edge technologies.The Journal of experimental medicine · 2024Review
- TL1A and IL-18 synergy promotes GM-CSF-dependent thymic granulopoiesis in mice.Cellular & molecular immunology · 2024Article
- The thymus road to a T cell: migration, selection, and atrophy.Frontiers in immunology · 2024Review
- Circulating IRF8-expressing CD123Trends in immunology · 2023Review
- Reading the Ts and DCs of thymopoiesis.Nature immunology · 2023Article
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Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cross-talk between thymocytes and thymic stromal cells is fundamental for T cell development. In humans, intrathymic development of dendritic cells (DCs) is evident but its physiological significance is unknown. Here we showed that DC-biased precursors depended on the expression of the transcription factor IRF8 to express the membrane-bound precursor form of the cytokine TNF (tmTNF) to promote differentiation of thymus seeding hematopoietic progenitors into T-lineage specified precursors through activation of the TNF receptor (TNFR)-2 instead of TNFR1. In vitro recapitulation of TNFR2 signaling by providing low-density tmTNF or a selective TNFR2 agonist enhanced the generation of human T cell precursors. Our study shows that, in addition to mediating thymocyte selection and maturation, DCs function as hematopoietic stromal support for the early stages of human T cell development and provide proof of concept that selective targeting of TNFR2 can enhance the in vitro generation of T cell precursors for clinical application.
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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.