ArticleThe Journal of experimental medicine2022
P2RY8 variants in lupus patients uncover a role for the receptor in immunological tolerance.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
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- HLA Class II Alleles DRB1*11:01 and DQB1*03:01 Unmask Immunogenetic Susceptibility to Anti-Nivolumab Antibodies in Combination with Ipilimumab.The AAPS journal · 2026Review
- Familial lupus associated with aJournal of human immunity · 2026Article
- Exome sequencing enables molecular diagnosis in 10% of early-onset or familial systemic lupus erythematosus cases.EBioMedicine · 2026Article
- Age-associated B-cells across the rheumatoid arthritis continuum: from early immunopathogenesis to comorbidities.Frontiers in aging · 2026Review
- Telomere-to-telomere genome assembly of a male pig provides insight into population structure and selection for body stature.Nature genetics · 2026Article
- Whole-genome profiling of age- and sex-associated DNA methylation signatures in human plasma cell-free DNA.Communications medicine · 2025Article
- Immune Checkpoint Signatures in Minimal Change Disease and Membranous Nephropathy: Divergent Pathways of a Shared Imbalance.International journal of molecular sciences · 2025Article
- Phenotypic pleiotropy of missense variants in human B cell confinement receptor P2RY8.Cell genomics · 2025Article
- WTAP Promotes the Excessive Proliferation of Airway Smooth Muscle Cells in Asthma by Enhancing AXIN1 Levels Through the Recognition of YTHDF2.Biochemical genetics · 2025Article
- Therapeutic progress in the targeting of B cells in lupus nephritis: pathogenesis to clinical research.International urology and nephrology · 2025Review
- Causal Inference and Shared Molecular Pathways in Crohn's Disease, Celiac Disease, and Ankylosing Spondylitis: Integrative Mendelian Randomization and Transcriptomic Analysis.International journal of molecular sciences · 2025Article
- Interferon signatures fuel B cell hyperactivity and plasmablast expansion in systemic lupus erythematosus.Journal of autoimmunity · 2025Article
- What's atypical about human B cells after allogeneic stem cell transplantation?Journal of leukocyte biology · 2025Review
- The regulatory functions of G protein-coupled receptors signaling pathways in B cell differentiation and development contributing to autoimmune diseases.Cell & bioscience · 2025Review
- Age-Associated B Cells in Autoimmune Diseases: Pathogenesis and Clinical Implications.Clinical reviews in allergy & immunology · 2025Review
- How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.ACR open rheumatology · 2025Review
- Towards precision medicine for systemic lupus erythematosus and neuropsychiatric manifestations.Expert review of precision medicine and drug development · 2025Article
- IFN-associated B cell hyperactivity is highly enriched in SLE patients harboring Sm/RNP antibodies.bioRxiv : the preprint server for biology · 2024Article
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28 authors at 5 institutions in 4 countries.
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Abstract
B cell self-tolerance is maintained through multiple checkpoints, including restraints on intracellular signaling and cell trafficking. P2RY8 is a receptor with established roles in germinal center (GC) B cell migration inhibition and growth regulation. Somatic P2RY8 variants are common in GC-derived B cell lymphomas. Here, we identify germline novel or rare P2RY8 missense variants in lupus kindreds or the related antiphospholipid syndrome, including a "de novo" variant in a child with severe nephritis. All variants decreased protein expression, F-actin abundance, and GPCR-RhoA signaling, and those with stronger effects increased AKT and ERK activity and cell migration. Remarkably, P2RY8 was reduced in B cell subsets from some SLE patients lacking P2RY8 gene variants. Low P2RY8 correlated with lupus nephritis and increased age-associated B cells and plasma cells. By contrast, P2RY8 overexpression in cells and mice restrained plasma cell development and reinforced negative selection of DNA-reactive developing B cells. These findings uncover a role of P2RY8 in immunological tolerance and lupus pathogenesis.
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