ArticleScience translational medicine2023
Inhibition of RIP1 improves immune reconstitution and reduces GVHD mortality while preserving graft-versus-leukemia effects.
Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- The multifaceted landscape of T cell exhaustion in organ transplantation: From molecular mechanisms (epigenetics, transcription, metabolism) to induction strategies.Genes & diseases · 2026Review
- The impact of T cell exhaustion in hematopoietic stem cell transplantation.Stem cell research & therapy · 2026Review
- TREM1-mediated macrophage activation drives voriconazole-induced hepatic steatosis: Diagnostic and therapeutic implications.Journal of pharmaceutical analysis · 2026Article
- [Fecal microbiota transplantation attenuates gastrointestinal inflammation in murine acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation by inhibiting RIPK1/RIPK3-mediated necroptosis].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Article
- Differential effects of GVHD therapies on intestinal epithelium.Blood advances · 2026Article
- Engineering polyphenol-based osteogenic system for bone and cartilage repair: Transplantation, tissue engineering, and organoid.Journal of advanced research · 2026Review
- A viable kinase-inactive RIPK3 D143N mouse model reveals its scaffold function in driving TNF-induced inflammatory disorder.Cell death discovery · 2026Article
- Discovery of SARS-CoV-2 PLpro inhibitors and RIPK1 inhibitors with synergistic antiviral efficacy in a mouse COVID-19 model.Acta pharmaceutica Sinica. B · 2026Article
- Targeting RIPK1 to modulate cell death and tumour microenvironment in cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Voriconazole-induced liver injury: incidence patterns and risk factors in a retrospective cohort.Antimicrobial agents and chemotherapy · 2025Article
- The Trim32-DPEP2 axis is an inflammatory switch in macrophages during intestinal inflammation.Cell death and differentiation · 2025Article
- The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications.Biomolecules · 2025Review
- Current status, challenges, and integration pathways of biomarker classification systems in graft-versus-host disease: a preliminary exploration.Frontiers in medicine · 2025Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Graft-versus-host disease (GVHD) remains the major cause of morbidity and nonrelapse mortality (NRM) after hematopoietic cell transplantation (HCT). Inflammatory cytokines mediate damage to key GVHD targets such as intestinal stem cells (ISCs) and also activate receptor interacting protein kinase 1 (RIP1; RIPK1), a critical regulator of apoptosis and necroptosis. We therefore investigated the role of RIP1 in acute GVHD using samples from HCT patients, modeling GVHD damage in vitro with both human and mouse gastrointestinal (GI) organoids, and blocking RIP1 activation in vivo using several well-characterized mouse HCT models. Increased phospho-RIP1 expression in GI biopsies from patients with acute GVHD correlated with tissue damage and predicted NRM. Both the genetic inactivation of RIP1 and the RIP1 inhibitor GNE684 prevented GVHD-induced apoptosis of ISCs in vivo and in vitro. Daily administration of GNE684 for 14 days reduced inflammatory infiltrates in three GVHD target organs (intestine, liver, and spleen) in mice. Unexpectedly, GNE684 administration also reversed the marked loss of regulatory T cells in the intestines and liver during GVHD and reduced splenic T cell exhaustion, thus improving immune reconstitution. Pharmacological and genetic inhibition of RIP1 improved long-term survival without compromising the graft-versus-leukemia (GVL) effect in lymphocytic and myeloid leukemia mouse models. Thus, RIP1inhibition may represent a nonimmunosuppressive treatment for GVHD.
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