ArticleThe Journal of clinical investigation2018
P2X7R mutation disrupts the NLRP3-mediated Th program and predicts poor cardiac allograft outcomes.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Latest advances on the role of P2X Receptors in colorectal inflammation and cancer.Purinergic signalling · 2026Review
- Heart Transplantation: Immunological Challenges Revisited.Current cardiology reviews · 2026Review
- P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis.Cell death & disease · 2025Article
- TMEM219 signaling promotes intestinal stem cell death and exacerbates colitis.The Journal of clinical investigation · 2025Article
- Pannexin-1 hemichannels promote experimental colitis inflammation in a CD4Frontiers in immunology · 2025Article
- Long non-coding RNA ENSMUST00000197208 promotes a shift in the Th17/Treg ratio via the P2X7R-NLRP3 inflammasome axis in collagen-induced arthritis.Immunologic research · 2024Article
- ATP-P2X7R pathway activation limits the Tfh cell compartment during pediatric RSV infection.Frontiers in immunology · 2024Article
- Article
- LncRNA SNHG16 regulates RAS and NF-κB pathway-mediated NLRP3 inflammasome activation to aggravate diabetes nephropathy through stabilizing TLR4.Acta diabetologica · 2023Article
- Inhibition of NLRP3 inflammasome activity by MCC950 leads to exacerbation of Sjӧgren's syndrome pathologies in non-obese diabetic mice.Immunology · 2023Article
- The role of extracellular ATP and P2X receptors in the pathogenesis of HIV-1.Current opinion in pharmacology · 2023Review
- USP1-regulated reciprocal differentiation of Th17 cells and Treg cells by deubiquitinating and stabilizing TAZ.Cellular & molecular immunology · 2023Article
- Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID-19.Diabetes/metabolism research and reviews · 2022Review
- The IGFBP3/TMEM219 pathway regulates beta cell homeostasis.Nature communications · 2022Article
- The Role of Purinergic Signaling in Heart Transplantation.Frontiers in immunology · 2022Review
- Extracellular ATP and Imbalance of CD4+ T Cell Compartment in Pediatric COVID-19.Frontiers in cellular and infection microbiology · 2022Article
- Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.Journal of endocrinological investigation · 2021Observational
- miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- P2X7 Receptor-Mediated Inflammation in Cardiovascular Disease.Frontiers in pharmacology · 2021Review
- Article
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Authors and funding
26 authors.
Funding
Abstract
Purinergic receptor-7 (P2X7R) signaling controls Th17 and Th1 generation/differentiation, while NOD-like receptor P3 (NLRP3) acts as a Th2 transcriptional factor. Here, we demonstrated the existence of a P2X7R/NLRP3 pathway in T cells that is dysregulated by a P2X7R intracellular region loss-of-function mutation, leading to NLRP3 displacement and to excessive Th17 generation due to abrogation of the NLRP3-mediated Th2 program. This ultimately resulted in poor outcomes in cardiac-transplanted patients carrying the mutant allele, who showed abnormal Th17 generation. Transient NLRP3 silencing in nonmutant T cells or overexpression in mutant T cells normalized the Th profile. Interestingly, IL-17 blockade reduced Th17 skewing of human T cells in vitro and abrogated the severe allograft vasculopathy and abnormal Th17 generation observed in preclinical models in which P2X7R was genetically deleted. This P2X7R intracellular region mutation thus impaired the modulatory effects of P2X7R on NLRP3 expression and function in T cells and led to NLRP3 dysregulation and Th17 skewing, delineating a high-risk group of cardiac-transplanted patients who may benefit from personalized therapy.
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