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Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength
In humans, high Notch activation promotes γδ T cell development, whereas lower levels promote αβ-lineage differentiation. How these different Notch signals are generated has remained unclear. We show that differential Notch receptor–ligand interactions mediate this process. Whereas Delta-like 4 supp...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620353/ https://www.ncbi.nlm.nih.gov/pubmed/23530123 http://dx.doi.org/10.1084/jem.20121798 |
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author | Van de Walle, Inge Waegemans, Els De Medts, Jelle De Smet, Greet De Smedt, Magda Snauwaert, Sylvia Vandekerckhove, Bart Kerre, Tessa Leclercq, Georges Plum, Jean Gridley, Thomas Wang, Tao Koch, Ute Radtke, Freddy Taghon, Tom |
author_facet | Van de Walle, Inge Waegemans, Els De Medts, Jelle De Smet, Greet De Smedt, Magda Snauwaert, Sylvia Vandekerckhove, Bart Kerre, Tessa Leclercq, Georges Plum, Jean Gridley, Thomas Wang, Tao Koch, Ute Radtke, Freddy Taghon, Tom |
author_sort | Van de Walle, Inge |
collection | PubMed |
description | In humans, high Notch activation promotes γδ T cell development, whereas lower levels promote αβ-lineage differentiation. How these different Notch signals are generated has remained unclear. We show that differential Notch receptor–ligand interactions mediate this process. Whereas Delta-like 4 supports both TCR-αβ and -γδ development, Jagged1 induces mainly αβ-lineage differentiation. In contrast, Jagged2-mediated Notch activation primarily results in γδ T cell development and represses αβ-lineage differentiation by inhibiting TCR-β formation. Consistently, TCR-αβ T cell development is rescued through transduction of a TCR-β transgene. Jagged2 induces the strongest Notch signal through interactions with both Notch1 and Notch3, whereas Delta-like 4 primarily binds Notch1. In agreement, Notch3 is a stronger Notch activator and only supports γδ T cell development, whereas Notch1 is a weaker activator supporting both TCR-αβ and -γδ development. Fetal thymus organ cultures in JAG2-deficient thymic lobes or with Notch3-blocking antibodies confirm the importance of Jagged2/Notch3 signaling in human TCR-γδ differentiation. Our findings reveal that differential Notch receptor–ligand interactions mediate human TCR-αβ and -γδ T cell differentiation and provide a mechanistic insight into the high Notch dependency of human γδ T cell development. |
format | Online Article Text |
id | pubmed-3620353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-36203532013-10-08 Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength Van de Walle, Inge Waegemans, Els De Medts, Jelle De Smet, Greet De Smedt, Magda Snauwaert, Sylvia Vandekerckhove, Bart Kerre, Tessa Leclercq, Georges Plum, Jean Gridley, Thomas Wang, Tao Koch, Ute Radtke, Freddy Taghon, Tom J Exp Med Article In humans, high Notch activation promotes γδ T cell development, whereas lower levels promote αβ-lineage differentiation. How these different Notch signals are generated has remained unclear. We show that differential Notch receptor–ligand interactions mediate this process. Whereas Delta-like 4 supports both TCR-αβ and -γδ development, Jagged1 induces mainly αβ-lineage differentiation. In contrast, Jagged2-mediated Notch activation primarily results in γδ T cell development and represses αβ-lineage differentiation by inhibiting TCR-β formation. Consistently, TCR-αβ T cell development is rescued through transduction of a TCR-β transgene. Jagged2 induces the strongest Notch signal through interactions with both Notch1 and Notch3, whereas Delta-like 4 primarily binds Notch1. In agreement, Notch3 is a stronger Notch activator and only supports γδ T cell development, whereas Notch1 is a weaker activator supporting both TCR-αβ and -γδ development. Fetal thymus organ cultures in JAG2-deficient thymic lobes or with Notch3-blocking antibodies confirm the importance of Jagged2/Notch3 signaling in human TCR-γδ differentiation. Our findings reveal that differential Notch receptor–ligand interactions mediate human TCR-αβ and -γδ T cell differentiation and provide a mechanistic insight into the high Notch dependency of human γδ T cell development. The Rockefeller University Press 2013-04-08 /pmc/articles/PMC3620353/ /pubmed/23530123 http://dx.doi.org/10.1084/jem.20121798 Text en © 2013 Van de Walle et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Van de Walle, Inge Waegemans, Els De Medts, Jelle De Smet, Greet De Smedt, Magda Snauwaert, Sylvia Vandekerckhove, Bart Kerre, Tessa Leclercq, Georges Plum, Jean Gridley, Thomas Wang, Tao Koch, Ute Radtke, Freddy Taghon, Tom Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength |
title | Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength |
title_full | Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength |
title_fullStr | Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength |
title_full_unstemmed | Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength |
title_short | Specific Notch receptor–ligand interactions control human TCR-αβ/γδ development by inducing differential Notch signal strength |
title_sort | specific notch receptor–ligand interactions control human tcr-αβ/γδ development by inducing differential notch signal strength |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620353/ https://www.ncbi.nlm.nih.gov/pubmed/23530123 http://dx.doi.org/10.1084/jem.20121798 |
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