Academic Bibliography

 Search 200 years of publications by Ghent University researchers.
Advanced search
1 file | 4.42 MB
Add to list
  1. Search results
  2. The Wiskott–Aldrich syndrome protein ...

The Wiskott–Aldrich syndrome protein is required for positive selection during T-cell lineage differentiation

Melissa Pille (UGent) , John Avila, Guillem Sanchez Sanchez, Glenn Goetgeluk (UGent) , Stijn De Munter (UGent) , Hanne Jansen, Lore Billiet (UGent) , Karin Weening (UGent) , Haipeng Xue, Sarah Bonte (UGent) , et al.
(2023) FRONTIERS IN IMMUNOLOGY. 14.
Author
Organization
Project
Abstract
The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immune deficiency caused by a mutation in the WAS gene. This leads to altered or absent WAS protein (WASp) expression and function resulting in thrombocytopenia, eczema, recurrent infections, and autoimmunity. In T cells, WASp is required for immune synapse formation. Patients with WAS show reduced numbers of peripheral blood T lymphocytes and an altered T-cell receptor repertoire. In vitro, their peripheral T cells show decreased proliferation and cytokine production upon aCD3/aCD28 stimulation. It is unclear whether these T-cell defects are acquired during peripheral activation or are, in part, generated during thymic development. Here, we assessed the role of WASp during T-cell differentiation using artificial thymic organoid cultures and in the thymus of humanized mice. Although CRISPR/Cas9 WAS knockout hematopoietic stem and progenitor cells (HSPCs) rearranged the T-cell receptor and differentiated to T-cell receptor (TCR)(+) CD4(+) CD8(+) double-positive (DP) cells similar to wild-type HSPCs, a partial defect in the generation of CD8 single-positive (SP) cells was observed, suggesting that WASp is involved in their positive selection. TCR repertoire analysis of the DP and CD8(+) SP population, however, showed a polyclonal repertoire with no bias toward autoreactivity. To our knowledge, this is the first study of the role of WASp in human T-cell differentiation and on TCR repertoire generation.
Keywords
Immunology, Immunology and Allergy, primary immunodeficiencies, INDEL, Cas9, CRISPR, ATO, T-cell repertoire, Wiskott Aldrich syndrome, T-cell development

Downloads

  • Download
    published version.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 4.42 MB

Citation

Please use this url to cite or link to this publication:

MLA
Pille, Melissa, et al. “The Wiskott–Aldrich Syndrome Protein Is Required for Positive Selection during T-Cell Lineage Differentiation.” FRONTIERS IN IMMUNOLOGY, vol. 14, Frontiers Media SA, 2023, doi:10.3389/fimmu.2023.1188099.
APA
Pille, M., Avila, J., Sanchez, G. S., Goetgeluk, G., De Munter, S., Jansen, H., … Vandekerckhove, B. (2023). The Wiskott–Aldrich syndrome protein is required for positive selection during T-cell lineage differentiation. FRONTIERS IN IMMUNOLOGY, 14. https://doi.org/10.3389/fimmu.2023.1188099
Chicago author-date
Pille, Melissa, John Avila, Guillem Sanchez Sanchez, Glenn Goetgeluk, Stijn De Munter, Hanne Jansen, Lore Billiet, et al. 2023. “The Wiskott–Aldrich Syndrome Protein Is Required for Positive Selection during T-Cell Lineage Differentiation.” FRONTIERS IN IMMUNOLOGY 14. https://doi.org/10.3389/fimmu.2023.1188099.
Chicago author-date (all authors)
Pille, Melissa, John Avila, Guillem Sanchez Sanchez, Glenn Goetgeluk, Stijn De Munter, Hanne Jansen, Lore Billiet, Karin Weening, Haipeng Xue, Sarah Bonte, Joline Ingels, Laurenz De Cock, Eva Pascal, Lucas Deseins, Tessa Kerre, Tom Taghon, Georges Leclercq, David Vermijlen, Brian Davis, and Bart Vandekerckhove. 2023. “The Wiskott–Aldrich Syndrome Protein Is Required for Positive Selection during T-Cell Lineage Differentiation.” FRONTIERS IN IMMUNOLOGY 14. doi:10.3389/fimmu.2023.1188099.
Vancouver
1.
Pille M, Avila J, Sanchez GS, Goetgeluk G, De Munter S, Jansen H, et al. The Wiskott–Aldrich syndrome protein is required for positive selection during T-cell lineage differentiation. FRONTIERS IN IMMUNOLOGY. 2023;14.
IEEE
[1]
M. Pille et al., “The Wiskott–Aldrich syndrome protein is required for positive selection during T-cell lineage differentiation,” FRONTIERS IN IMMUNOLOGY, vol. 14, 2023.
@article{01H3A8ES0S9QKGDRSCB5RKPY83,
  abstract     = {{The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immune deficiency caused by a mutation in the WAS gene. This leads to altered or absent WAS protein (WASp) expression and function resulting in thrombocytopenia, eczema, recurrent infections, and autoimmunity. In T cells, WASp is required for immune synapse formation. Patients with WAS show reduced numbers of peripheral blood T lymphocytes and an altered T-cell receptor repertoire. In vitro, their peripheral T cells show decreased proliferation and cytokine production upon aCD3/aCD28 stimulation. It is unclear whether these T-cell defects are acquired during peripheral activation or are, in part, generated during thymic development. Here, we assessed the role of WASp during T-cell differentiation using artificial thymic organoid cultures and in the thymus of humanized mice. Although CRISPR/Cas9 WAS knockout hematopoietic stem and progenitor cells (HSPCs) rearranged the T-cell receptor and differentiated to T-cell receptor (TCR)(+) CD4(+) CD8(+) double-positive (DP) cells similar to wild-type HSPCs, a partial defect in the generation of CD8 single-positive (SP) cells was observed, suggesting that WASp is involved in their positive selection. TCR repertoire analysis of the DP and CD8(+) SP population, however, showed a polyclonal repertoire with no bias toward autoreactivity. To our knowledge, this is the first study of the role of WASp in human T-cell differentiation and on TCR repertoire generation.}},
  articleno    = {{1188099}},
  author       = {{Pille, Melissa and Avila, John and Sanchez, Guillem Sanchez and Goetgeluk, Glenn and De Munter, Stijn and Jansen, Hanne and Billiet, Lore and Weening, Karin and Xue, Haipeng and Bonte, Sarah and Ingels, Joline and De Cock, Laurenz and Pascal, Eva and Deseins, Lucas and Kerre, Tessa and Taghon, Tom and Leclercq, Georges and Vermijlen, David and Davis, Brian and Vandekerckhove, Bart}},
  issn         = {{1664-3224}},
  journal      = {{FRONTIERS IN IMMUNOLOGY}},
  keywords     = {{Immunology,Immunology and Allergy,primary immunodeficiencies,INDEL,Cas9,CRISPR,ATO,T-cell repertoire,Wiskott Aldrich syndrome,T-cell development}},
  language     = {{eng}},
  pages        = {{13}},
  publisher    = {{Frontiers Media SA}},
  title        = {{The Wiskott–Aldrich syndrome protein is required for positive selection during T-cell lineage differentiation}},
  url          = {{http://doi.org/10.3389/fimmu.2023.1188099}},
  volume       = {{14}},
  year         = {{2023}},
}
Altmetric
View in Altmetric
Web of Science
Times cited: