Single-cell profiling identifies a spectrum of human unconventional intraepithelial T lineage cells
Single-cell profiling identifies a spectrum of human unconventional intraepithelial T lineage cells
Abstract In the human thymus, a CD10+ PD-1+ TCRαβ+ differentiation pathway diverges from the conventional single positive T cell lineages at the early double positive stage. These cells are phenotypically and functionally similar to murine unconventional intraepithelial lymphocyte (uIEL) precursors. Here, the progeny of the human uIEL lineage was identified in antigen-inexperienced blood. The uIELs in thymus and peripheral blood share a transcriptomic profile, characterized by hallmark transcription factors (i.e. ZNF683 and IKZF2), and polyclonal TCR repertoire with autoreactive features, exhibiting a bias towards early TCR alpha chain rearrangements. Single-cell RNA sequencing confirmed a common developmental trajectory between the thymic and peripheral uIELs, and clearly delineated this unconventional lineage in peripheral blood. This population is phenotypically defined as CD3+ TCRαβ+ CD4- CCR7- CD26-. It contains CD10+ recent thymic emigrants, Helios+ KIR+ CD8+ Tregs and CD8αα+ T cells. Thus, the uIEL lineage represents a well-defined but heterogeneous, unconventional TCRαβ+ lineage mostly confined in human within the CD8 single positive T cells. SummaryBilliet et al. identify the postthymic progeny of the intraepithelial lymphocyte precursors in human based on shared characteristics of the T cell receptor repertoire and the transcriptome. This lineage represents a well-defined but heterogeneous, unconventional TCRαβ+ lineage mostly confined within the CD8 single positive T cells.
Kerre Tessa、Vandamme Niels、Impens Francis、Sanchez Guillem Sanchez、Mayer Rupert L.、Pille Melissa、Vermijlen David、Vandekerckhhove Bart、Van Nieuwerburgh Filip、Menten Bj?rn、Leclercq Georges、Weening Karin、Goetgeluk Glenn、Lavaert Marieke、De Munter Stijn、Ingels Joline、Taghon Tom、Pascal Eva、Billiet Lore、Bonte Sarah、Raes Killian、De Cock Laurenz、Roels Jana、Seurinck Ruth、Jansen Hanne
Department of Diagnostic Sciences, Ghent University||Cancer Research Institute Ghent (CRIG)||Department of Internal Medicine and Pediatrics, Ghent UniversityVIB Single Cell Core, VIB||Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation ResearchDepartment of Biomolecular Medicine, Ghent University||VIB-UGent Center for Medical Biotechnology, VIB||VIB Proteomics Core, VIBDepartment of Pharmacotherapy and Pharmaceutics, Universit¨| Libre de Bruxelles (ULB)||Institute for Medical Immunology, Universit¨| Libre de Bruxelles (ULB)||ULB Center for Research in Immunology (U-CRI), Universit¨| Libre de Bruxelles (ULB)Department of Biomolecular Medicine, Ghent University||VIB-UGent Center for Medical Biotechnology, VIB||VIB Proteomics Core, VIBDepartment of Diagnostic Sciences, Ghent UniversityDepartment of Pharmacotherapy and Pharmaceutics, Universit¨| Libre de Bruxelles (ULB)||Institute for Medical Immunology, Universit¨| Libre de Bruxelles (ULB)||ULB Center for Research in Immunology (U-CRI), Universit¨| Libre de Bruxelles (ULB)Department of Diagnostic Sciences, Ghent University||Cancer Research Institute Ghent (CRIG)Cancer Research Institute Ghent (CRIG)||Department of Pharmaceutics, Ghent UniversityDepartment of Biomolecular Medicine, Ghent UniversityDepartment of Diagnostic Sciences, Ghent University||Cancer Research Institute Ghent (CRIG)Department of Diagnostic Sciences, Ghent UniversityDepartment of Diagnostic Sciences, Ghent University||Cancer Research Institute Ghent (CRIG)Department of Diagnostic Sciences, Ghent UniversityDepartment of Diagnostic Sciences, Ghent University||Cancer Research Institute Ghent (CRIG)Department of Diagnostic Sciences, Ghent University||Cancer Research Institute Ghent (CRIG)Department of Diagnostic Sciences, Ghent University||Cancer Research Institute Ghent (CRIG)Department of Diagnostic Sciences, Ghent University||Cancer Research Institute Ghent (CRIG)Department of Diagnostic Sciences, Ghent UniversityCancer Research Institute Ghent (CRIG)||Department of Internal Medicine and Pediatrics, Ghent University||Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation ResearchDepartment of Diagnostic Sciences, Ghent UniversityDepartment of Biomolecular Medicine, Ghent University||Cancer Research Institute Ghent (CRIG)VIB Single Cell Core, VIB||Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation ResearchData Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation ResearchDepartment of Diagnostic Sciences, Ghent University
基础医学细胞生物学分子生物学
Kerre Tessa,Vandamme Niels,Impens Francis,Sanchez Guillem Sanchez,Mayer Rupert L.,Pille Melissa,Vermijlen David,Vandekerckhhove Bart,Van Nieuwerburgh Filip,Menten Bj?rn,Leclercq Georges,Weening Karin,Goetgeluk Glenn,Lavaert Marieke,De Munter Stijn,Ingels Joline,Taghon Tom,Pascal Eva,Billiet Lore,Bonte Sarah,Raes Killian,De Cock Laurenz,Roels Jana,Seurinck Ruth,Jansen Hanne.Single-cell profiling identifies a spectrum of human unconventional intraepithelial T lineage cells[EB/OL].(2025-03-28)[2025-06-01].https://www.biorxiv.org/content/10.1101/2022.05.24.492634.点此复制
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