Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF
- Author
- Kai Ling Liang (UGent) , Juliette Roels (UGent) , Marieke Lavaert, Tom Putteman (UGent) , Lena Böhme (UGent) , Laurentijn Tilleman (UGent) , Imke Velghe (UGent) , Valentina Pegoretti, Inge Van de Walle (UGent) , Stephanie Sontag, Jolien Vandewalle (UGent) , Bart Vandekerckhove (UGent) , Georges Leclercq (UGent) , Pieter Van Vlierberghe (UGent) , Claude Libert (UGent) , Filip Van Nieuwerburgh (UGent) , Roman Fischer, Roland E. Kontermann, Klaus Pfizenmaier, Gina Doody, Martin Zenke and Tom Taghon (UGent)
- Organization
- Project
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- GATA-3: a novel tumor suppressor gene during human T cell development
- Origin and molecular drivers of T cell and dendritic cell development in the human thymus.
- Single cell approaches for the study of early human T cell development
- Unravelling cellular heterogeneity and dynamics in normal and malignant hematopoiesis using singlecell bioinformatics
- Characterisation of the oncogenic mechanisms induced by GATA3 mutations in cancer.
- Unraveling the role of GATA3 in BCP-ALL
- Cofunding core facility - Flow cytometry
- HPC-UGent: the central High Performance Computing infrastructure of Ghent University
- Epigenetic drivers of human αβ and γδ T cell differentiation at the single cell level.
- 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. In humans, intrathymic development of DCs is evident but its physiological significance is unknown. Taghon et al. show intrathymic development of DCs as hematopoietic stromal support for the early stages of human T cell development via IRF8-driven transmembrane TNF.
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01H3YHH484PETM0VQGKPKJTXKM
- MLA
- Liang, Kai Ling, et al. “Intrathymic Dendritic Cell-Biased Precursors Promote Human T Cell Lineage Specification through IRF8-Driven Transmembrane TNF.” NATURE IMMUNOLOGY, vol. 24, no. 3, 2023, pp. 474–86, doi:10.1038/s41590-022-01417-6.
- APA
- Liang, K. L., Roels, J., Lavaert, M., Putteman, T., Böhme, L., Tilleman, L., … Taghon, T. (2023). Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF. NATURE IMMUNOLOGY, 24(3), 474–486. https://doi.org/10.1038/s41590-022-01417-6
- Chicago author-date
- Liang, Kai Ling, Juliette Roels, Marieke Lavaert, Tom Putteman, Lena Böhme, Laurentijn Tilleman, Imke Velghe, et al. 2023. “Intrathymic Dendritic Cell-Biased Precursors Promote Human T Cell Lineage Specification through IRF8-Driven Transmembrane TNF.” NATURE IMMUNOLOGY 24 (3): 474–86. https://doi.org/10.1038/s41590-022-01417-6.
- Chicago author-date (all authors)
- Liang, Kai Ling, Juliette Roels, Marieke Lavaert, Tom Putteman, Lena Böhme, Laurentijn Tilleman, Imke Velghe, Valentina Pegoretti, Inge Van de Walle, Stephanie Sontag, Jolien Vandewalle, Bart Vandekerckhove, Georges Leclercq, Pieter Van Vlierberghe, Claude Libert, Filip Van Nieuwerburgh, Roman Fischer, Roland E. Kontermann, Klaus Pfizenmaier, Gina Doody, Martin Zenke, and Tom Taghon. 2023. “Intrathymic Dendritic Cell-Biased Precursors Promote Human T Cell Lineage Specification through IRF8-Driven Transmembrane TNF.” NATURE IMMUNOLOGY 24 (3): 474–486. doi:10.1038/s41590-022-01417-6.
- Vancouver
- 1.Liang KL, Roels J, Lavaert M, Putteman T, Böhme L, Tilleman L, et al. Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF. NATURE IMMUNOLOGY. 2023;24(3):474–86.
- IEEE
- [1]K. L. Liang et al., “Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF,” NATURE IMMUNOLOGY, vol. 24, no. 3, pp. 474–486, 2023.
@article{01H3YHH484PETM0VQGKPKJTXKM,
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.
In humans, intrathymic development of DCs is evident but its physiological significance is unknown. Taghon et al. show intrathymic development of DCs as hematopoietic stromal support for the early stages of human T cell development via IRF8-driven transmembrane TNF.}},
author = {{Liang, Kai Ling and Roels, Juliette and Lavaert, Marieke and Putteman, Tom and Böhme, Lena and Tilleman, Laurentijn and Velghe, Imke and Pegoretti, Valentina and Van de Walle, Inge and Sontag, Stephanie and Vandewalle, Jolien and Vandekerckhove, Bart and Leclercq, Georges and Van Vlierberghe, Pieter and Libert, Claude and Van Nieuwerburgh, Filip and Fischer, Roman and Kontermann, Roland E. and Pfizenmaier, Klaus and Doody, Gina and Zenke, Martin and Taghon, Tom}},
issn = {{1529-2908}},
journal = {{NATURE IMMUNOLOGY}},
language = {{eng}},
number = {{3}},
pages = {{474--486}},
title = {{Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF}},
url = {{http://doi.org/10.1038/s41590-022-01417-6}},
volume = {{24}},
year = {{2023}},
}
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