학술논문
Intrathymic dendritic cell-biased precursors promote human T cell lineage specification through IRF8-driven transmembrane TNF.
Document Type
Academic Journal
Author
Liang KL; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent, Ghent, Belgium.; Roels J; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Genentech Inc., South San Francisco, CA, USA.; Lavaert M; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.; Putteman T; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Boehme L; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Tilleman L; Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.; Velghe I; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Pegoretti V; Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.; Van de Walle I; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; argenx BVBA, Zwijnaarde, Belgium.; Sontag S; Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.; Vandewalle J; VIB Center for Inflammation Research (IRC), Technologiepark, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.; Vandekerckhove B; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent, Ghent, Belgium.; Leclercq G; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent, Ghent, Belgium.; Van Vlierberghe P; Cancer Research Institute Ghent, Ghent, Belgium.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.; Libert C; VIB Center for Inflammation Research (IRC), Technologiepark, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.; Van Nieuwerburgh F; Cancer Research Institute Ghent, Ghent, Belgium.; Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.; Fischer R; Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.; BioNtech, Mainz, Germany.; Kontermann RE; Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.; Pfizenmaier K; Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.; Doody G; Leeds Institute of Medical Research, University of Leeds, Leeds, UK.; Zenke M; Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.; Taghon T; Department of Diagnostic Sciences, Ghent University, Ghent, Belgium. tom.taghon@ugent.be.; Cancer Research Institute Ghent, Ghent, Belgium. tom.taghon@ugent.be.
Source
Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE
Subject
Language
English
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.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)