RIPK1 ablation in T cells results in spontaneous enteropathy and TNF-driven villus atrophy
- Author
- Jelle Huysentruyt, Wolf Steels, Mario Ruiz Pérez, Bruno Verstraeten (UGent) , Tatyana Divert (UGent) , Kayleigh Flies, Kelly Lemeire (UGent) , Nozomi Takahashi (UGent) , Elke De Bruyn (UGent) , Marie Joossens (UGent) , Andrew Brown (UGent) , Bart Lambrecht (UGent) , Wim Declercq (UGent) , Tom Vanden Berghe (UGent) , Jonathan Maelfait (UGent) , Peter Vandenabeele (UGent) and Peter Tougaard (UGent)
- Organization
- Project
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- RIPK1 in T-cells: an interplay between cell death signalling and immunity
- DR3 – a Novel Inducer of Necroptosis and Mediator of Intestinal Inflammation and Pathology
- Thymic reprogramming: Systemic inflammation changes the cellular output of the thymus from T cells to NK cells and iron-binding myeloid cells
- Investigating the role of ferroptosis in acute liver injury and multiple sclerosis with newly developed chemical tool compounds
- Thymic reprogramming: The role of Death Receptor 3 (DR3)
- Factors that determine RIPK1-dependent necroptosis
- 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
- Cell death modality regulation during immunotherapy (CREDIT): molecular mechanisms and experimental therapy.
- Unraveling the in vivo role of RIPK1: Physiological and pathological consequences of kinase-dependent and kinase-independent functions
- Abstract
- RIPK1 is a crucial regulator of cell survival, inflammation and cell death. Human RIPK1 deficiency leads to early-onset intestinal inflammation and peripheral T cell imbalance, though its role in alpha beta T cell-mediated intestinal homeostasis remains unclear. In this study, we demonstrate that mice with RIPK1 ablation in conventional alpha beta T cells (Ripk1 Delta CD4) developed a severe small intestinal pathology characterized by small intestinal elongation, crypt hyperplasia, and duodenum-specific villus atrophy. Using mixed bone marrow chimeras reveals a survival disadvantage of alpha beta T cells compared to gamma delta T cells in the small intestine. Broad-spectrum antibiotic treatment ameliorates crypt hyperplasia and prevents intestinal elongation, though villus atrophy persists. Conversely, crossing Ripk1 Delta CD4 with TNF receptor 1 Tnfr1-/- knockout mice rescues villus atrophy but not intestinal elongation. Finally, combined ablation of Ripk1 triangle CD4 and Casp8 triangle CD4 fully rescues intestinal pathology, revealing that alpha beta T cell apoptosis in Ripk1 triangle CD4 drives the enteropathy. These findings demonstrate that RIPK1-mediated survival of alpha beta T cells is essential for proximal small intestinal homeostasis. In Ripk1 triangle CD4 mice, the imbalanced T cell compartment drives microbiome-mediated intestinal elongation and TNF-driven villus atrophy.
- Keywords
- Caspase-8, TNFR1, Duodenal Pathology, T Cell Imbalance, Intestinal Epithelial Layer, INTRAEPITHELIAL LYMPHOCYTES, REGIONAL SPECIALIZATION, EPITHELIAL HOMEOSTASIS, CELIAC-DISEASE, CUTTING EDGE, MUTATIONS, CASPASE-8, INFLAMMATION, NECROPTOSIS, DEFICIENT
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01JWZMF9CDMVQBA53GVZ8XMTVZ
- MLA
- Huysentruyt, Jelle, et al. “RIPK1 Ablation in T Cells Results in Spontaneous Enteropathy and TNF-Driven Villus Atrophy.” EMBO REPORTS, vol. 26, no. 10, 2025, pp. 2654–82, doi:10.1038/s44319-025-00441-5.
- APA
- Huysentruyt, J., Steels, W., Ruiz Pérez, M., Verstraeten, B., Divert, T., Flies, K., … Tougaard, P. (2025). RIPK1 ablation in T cells results in spontaneous enteropathy and TNF-driven villus atrophy. EMBO REPORTS, 26(10), 2654–2682. https://doi.org/10.1038/s44319-025-00441-5
- Chicago author-date
- Huysentruyt, Jelle, Wolf Steels, Mario Ruiz Pérez, Bruno Verstraeten, Tatyana Divert, Kayleigh Flies, Kelly Lemeire, et al. 2025. “RIPK1 Ablation in T Cells Results in Spontaneous Enteropathy and TNF-Driven Villus Atrophy.” EMBO REPORTS 26 (10): 2654–82. https://doi.org/10.1038/s44319-025-00441-5.
- Chicago author-date (all authors)
- Huysentruyt, Jelle, Wolf Steels, Mario Ruiz Pérez, Bruno Verstraeten, Tatyana Divert, Kayleigh Flies, Kelly Lemeire, Nozomi Takahashi, Elke De Bruyn, Marie Joossens, Andrew Brown, Bart Lambrecht, Wim Declercq, Tom Vanden Berghe, Jonathan Maelfait, Peter Vandenabeele, and Peter Tougaard. 2025. “RIPK1 Ablation in T Cells Results in Spontaneous Enteropathy and TNF-Driven Villus Atrophy.” EMBO REPORTS 26 (10): 2654–2682. doi:10.1038/s44319-025-00441-5.
- Vancouver
- 1.Huysentruyt J, Steels W, Ruiz Pérez M, Verstraeten B, Divert T, Flies K, et al. RIPK1 ablation in T cells results in spontaneous enteropathy and TNF-driven villus atrophy. EMBO REPORTS. 2025;26(10):2654–82.
- IEEE
- [1]J. Huysentruyt et al., “RIPK1 ablation in T cells results in spontaneous enteropathy and TNF-driven villus atrophy,” EMBO REPORTS, vol. 26, no. 10, pp. 2654–2682, 2025.
@article{01JWZMF9CDMVQBA53GVZ8XMTVZ,
abstract = {{RIPK1 is a crucial regulator of cell survival, inflammation and cell death. Human RIPK1 deficiency leads to early-onset intestinal inflammation and peripheral T cell imbalance, though its role in alpha beta T cell-mediated intestinal homeostasis remains unclear. In this study, we demonstrate that mice with RIPK1 ablation in conventional alpha beta T cells (Ripk1 Delta CD4) developed a severe small intestinal pathology characterized by small intestinal elongation, crypt hyperplasia, and duodenum-specific villus atrophy. Using mixed bone marrow chimeras reveals a survival disadvantage of alpha beta T cells compared to gamma delta T cells in the small intestine. Broad-spectrum antibiotic treatment ameliorates crypt hyperplasia and prevents intestinal elongation, though villus atrophy persists. Conversely, crossing Ripk1 Delta CD4 with TNF receptor 1 Tnfr1-/- knockout mice rescues villus atrophy but not intestinal elongation. Finally, combined ablation of Ripk1 triangle CD4 and Casp8 triangle CD4 fully rescues intestinal pathology, revealing that alpha beta T cell apoptosis in Ripk1 triangle CD4 drives the enteropathy. These findings demonstrate that RIPK1-mediated survival of alpha beta T cells is essential for proximal small intestinal homeostasis. In Ripk1 triangle CD4 mice, the imbalanced T cell compartment drives microbiome-mediated intestinal elongation and TNF-driven villus atrophy.}},
author = {{Huysentruyt, Jelle and Steels, Wolf and Ruiz Pérez, Mario and Verstraeten, Bruno and Divert, Tatyana and Flies, Kayleigh and Lemeire, Kelly and Takahashi, Nozomi and De Bruyn, Elke and Joossens, Marie and Brown, Andrew and Lambrecht, Bart and Declercq, Wim and Vanden Berghe, Tom and Maelfait, Jonathan and Vandenabeele, Peter and Tougaard, Peter}},
issn = {{1469-221X}},
journal = {{EMBO REPORTS}},
keywords = {{Caspase-8,TNFR1,Duodenal Pathology,T Cell Imbalance,Intestinal Epithelial Layer,INTRAEPITHELIAL LYMPHOCYTES,REGIONAL SPECIALIZATION,EPITHELIAL HOMEOSTASIS,CELIAC-DISEASE,CUTTING EDGE,MUTATIONS,CASPASE-8,INFLAMMATION,NECROPTOSIS,DEFICIENT}},
language = {{eng}},
number = {{10}},
pages = {{2654--2682}},
title = {{RIPK1 ablation in T cells results in spontaneous enteropathy and TNF-driven villus atrophy}},
url = {{http://doi.org/10.1038/s44319-025-00441-5}},
volume = {{26}},
year = {{2025}},
}
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