RIPK1 protects naive and regulatory T cells from TNFR1-induced apoptosis
- Author
- Jelle Huysentruyt, Wolf Steels, Mario Ruiz Pérez, Bruno Verstraeten (UGent) , Mike Vadi (UGent) , Tatyana Divert (UGent) , Kayleigh Flies, Nozomi Takahashi (UGent) , Bart Lambrecht (UGent) , Wim Declercq (UGent) , Tom Vanden Berghe (UGent) , Jonathan Maelfait (UGent) , Peter Vandenabeele (UGent) and Peter Tougaard (UGent)
- Organization
- Project
-
- RIPK1 in T-cells: an interplay between cell death signalling and immunity
- Elucidate the role of death receptor 3 (DR3) in thymic immune activation in infectious disease
- Thymic reprogramming: Systemic inflammation changes the cellular output of the thymus from T cells to NK cells and iron-binding myeloid cells
- DR3 – a Novel Inducer of Necroptosis and Mediator of Intestinal Inflammation and Pathology
- Thymic reprogramming: The role of Death Receptor 3 (DR3)
- MOlecular mechanisms of cellular DEath and Life decisions in Inflammation, Degeneration and Infection
- Cell Death Regulation and Role in Infection and Inflammatory Diseases
- Cell death activity regulation in inflammation and cancer
- Autophagy in inflammation and inflammatory disorders (ATLANTIS), from basic insights to experimental therapy
- Improving cancer therapy by modulating cell death and the microbiome in the gut
- De BD FACS Symphony FACS cell sorter : de meest geavanceerde multiparameter fluorescentie geactiveerde cell sorter die de indetificatie en purificatie van zeldzame cellen toelaat voor verdere functionele characterisatie
- Purchase steam autoclave central kitchen Department of Biomedical Molecular Biology
- Replacement and extension of basic infrastructure in the histology core facility.
- Dissecting the role of RIPK4 in skin cancer
- Abstract
- The T cell population size is stringently controlled before, during, and after immune responses, as improper cell death regulation can result in autoimmunity and immunodeficiency. RIPK1 is an important regulator of peripheral T cell survival and homeostasis. However, whether different peripheral T cell subsets show a differential requirement for RIPK1 and which programmed cell death pathway they engage in vivo remains unclear. In this study, we demonstrate that conditional ablation of Ripk1 in conventional T cells (Ripk1 Delta CD4) causes peripheral T cell lymphopenia, as witnessed by a profound loss of naive CD4+, naive CD8+, and FoxP3+ regulatory T cells. Interestingly, peripheral naive CD8+ T cells in Ripk1 Delta CD4 mice appear to undergo a selective pressure to retain RIPK1 expression following activation. Mixed bone marrow chimeras revealed a competitive survival disadvantage for naive, effector, and memory T cells lacking RIPK1. Additionally, tamoxifen-induced deletion of RIPK1 in CD4-expressing cells in adult life confirmed the importance of RIPK1 in post-thymic survival of CD4+ T cells. Ripk1 K45A mice showed no change in peripheral T cell subsets, demonstrating that the T cell lymphopenia was due to the scaffold function of RIPK1 rather than to its kinase activity. Enhanced numbers of Ripk1 Delta CD4 naive T cells expressed the proliferation marker Ki-67+ despite the peripheral lymphopenia and single-cell RNA sequencing revealed T cell-specific transcriptomic alterations that were reverted by additional caspase-8 deficiency. Furthermore, Ripk1 Delta CD4 Casp8 Delta CD4 and Ripk1 Delta CD4 Tnfr1 -/- double-knockout mice rescued the peripheral T cell lymphopenia, revealing that RIPK1-deficient naive CD4+ and CD8+ cells and FoxP3+ regulatory T cells specifically die from TNF- and caspase-8-mediated apoptosis in vivo. Altogether, our findings emphasize the essential role of RIPK1 as a scaffold in maintaining the peripheral T cell compartment and preventing TNFR1-induced apoptosis.
Downloads
-
s41418-024-01301-w.pdf
- full text (Published version)
- |
- open access
- |
- |
- 4.47 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HZ4EB4G5NJ2Z17F8DTYRHGTM
- MLA
- Huysentruyt, Jelle, et al. “RIPK1 Protects Naive and Regulatory T Cells from TNFR1-Induced Apoptosis.” CELL DEATH AND DIFFERENTIATION, vol. 31, 2024, pp. 820–32, doi:10.1038/s41418-024-01301-w.
- APA
- Huysentruyt, J., Steels, W., Ruiz Pérez, M., Verstraeten, B., Vadi, M., Divert, T., … Tougaard, P. (2024). RIPK1 protects naive and regulatory T cells from TNFR1-induced apoptosis. CELL DEATH AND DIFFERENTIATION, 31, 820–832. https://doi.org/10.1038/s41418-024-01301-w
- Chicago author-date
- Huysentruyt, Jelle, Wolf Steels, Mario Ruiz Pérez, Bruno Verstraeten, Mike Vadi, Tatyana Divert, Kayleigh Flies, et al. 2024. “RIPK1 Protects Naive and Regulatory T Cells from TNFR1-Induced Apoptosis.” CELL DEATH AND DIFFERENTIATION 31: 820–32. https://doi.org/10.1038/s41418-024-01301-w.
- Chicago author-date (all authors)
- Huysentruyt, Jelle, Wolf Steels, Mario Ruiz Pérez, Bruno Verstraeten, Mike Vadi, Tatyana Divert, Kayleigh Flies, Nozomi Takahashi, Bart Lambrecht, Wim Declercq, Tom Vanden Berghe, Jonathan Maelfait, Peter Vandenabeele, and Peter Tougaard. 2024. “RIPK1 Protects Naive and Regulatory T Cells from TNFR1-Induced Apoptosis.” CELL DEATH AND DIFFERENTIATION 31: 820–832. doi:10.1038/s41418-024-01301-w.
- Vancouver
- 1.Huysentruyt J, Steels W, Ruiz Pérez M, Verstraeten B, Vadi M, Divert T, et al. RIPK1 protects naive and regulatory T cells from TNFR1-induced apoptosis. CELL DEATH AND DIFFERENTIATION. 2024;31:820–32.
- IEEE
- [1]J. Huysentruyt et al., “RIPK1 protects naive and regulatory T cells from TNFR1-induced apoptosis,” CELL DEATH AND DIFFERENTIATION, vol. 31, pp. 820–832, 2024.
@article{01HZ4EB4G5NJ2Z17F8DTYRHGTM,
abstract = {{The T cell population size is stringently controlled before, during, and after immune responses, as improper cell death regulation can result in autoimmunity and immunodeficiency. RIPK1 is an important regulator of peripheral T cell survival and homeostasis. However, whether different peripheral T cell subsets show a differential requirement for RIPK1 and which programmed cell death pathway they engage in vivo remains unclear. In this study, we demonstrate that conditional ablation of Ripk1 in conventional T cells (Ripk1 Delta CD4) causes peripheral T cell lymphopenia, as witnessed by a profound loss of naive CD4+, naive CD8+, and FoxP3+ regulatory T cells. Interestingly, peripheral naive CD8+ T cells in Ripk1 Delta CD4 mice appear to undergo a selective pressure to retain RIPK1 expression following activation. Mixed bone marrow chimeras revealed a competitive survival disadvantage for naive, effector, and memory T cells lacking RIPK1. Additionally, tamoxifen-induced deletion of RIPK1 in CD4-expressing cells in adult life confirmed the importance of RIPK1 in post-thymic survival of CD4+ T cells. Ripk1 K45A mice showed no change in peripheral T cell subsets, demonstrating that the T cell lymphopenia was due to the scaffold function of RIPK1 rather than to its kinase activity. Enhanced numbers of Ripk1 Delta CD4 naive T cells expressed the proliferation marker Ki-67+ despite the peripheral lymphopenia and single-cell RNA sequencing revealed T cell-specific transcriptomic alterations that were reverted by additional caspase-8 deficiency. Furthermore, Ripk1 Delta CD4 Casp8 Delta CD4 and Ripk1 Delta CD4 Tnfr1 -/- double-knockout mice rescued the peripheral T cell lymphopenia, revealing that RIPK1-deficient naive CD4+ and CD8+ cells and FoxP3+ regulatory T cells specifically die from TNF- and caspase-8-mediated apoptosis in vivo. Altogether, our findings emphasize the essential role of RIPK1 as a scaffold in maintaining the peripheral T cell compartment and preventing TNFR1-induced apoptosis.}},
author = {{Huysentruyt, Jelle and Steels, Wolf and Ruiz Pérez, Mario and Verstraeten, Bruno and Vadi, Mike and Divert, Tatyana and Flies, Kayleigh and Takahashi, Nozomi and Lambrecht, Bart and Declercq, Wim and Vanden Berghe, Tom and Maelfait, Jonathan and Vandenabeele, Peter and Tougaard, Peter}},
issn = {{1350-9047}},
journal = {{CELL DEATH AND DIFFERENTIATION}},
language = {{eng}},
pages = {{820--832}},
title = {{RIPK1 protects naive and regulatory T cells from TNFR1-induced apoptosis}},
url = {{http://doi.org/10.1038/s41418-024-01301-w}},
volume = {{31}},
year = {{2024}},
}
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: