ArticleScience advances2022
ATR-mediated DNA damage responses underlie aberrant B cell activity in systemic lupus erythematosus.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Sublethal DNA damage switches off B cell effector programs in an RA-FLS-PBMC co-culture.Cell death discovery · 2026Article
- Upregulated ZBP1 Is Associated with B-Cell Dysregulation in Systemic Lupus Erythematosus.Biomedicines · 2026Article
- IFNγ-induced IRF1 synergizes with TLR7 signals to tune the IRF4-IRF8 axis and drive pathogenic effector B cell fate.bioRxiv : the preprint server for biology · 2026Article
- Review
- DNA damage in macrophages drives immune autoreactivity via nuclear antigen presentation.Nature aging · 2026Article
- Accelerated immunosenescence in SLE: current evidence and clinical translation.Frontiers in immunology · 2026Review
- Augmentation of DNA exonuclease TREX1 in macrophages as a therapy for cardiac ischemic injury.Science translational medicine · 2025Article
- Implications of DNA damage response and immunotherapy in tumor therapy.Cell communication and signaling : CCS · 2025Review
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- DNAzyme targeting RIP3 suppresses NLRP3-mediated necroinflammation for the treatment of inflammatory diseases.Acta pharmaceutica Sinica. B · 2025Article
- Immune cells in systemic lupus erythematosus: biology and traditional Chinese medicine therapy.Acta pharmacologica Sinica · 2025Review
- Transcriptome analysis to decipher the molecular underpinnings of response to treatment in systemic lupus erythematosus.RMD open · 2025Article
- DDIT3 deficiency ameliorates systemic lupus erythematosus by regulating B cell activation and differentiation.Life medicine · 2025Article
- Increased interferon I signaling, DNA damage response and evidence of T-cell exhaustion in a patient with combined interferonopathy (Aicardi-Goutières Syndrome, AGS) and cohesinopathy (Cornelia de Lange Syndrome, CdLS).Pediatric rheumatology online journal · 2025Article
- Plasma cell-free DNA genome-wide methylation profiling enables detection and activity assessment in systemic lupus erythematosus.Frontiers in immunology · 2025Article
- Myeloid cells as IFNα producers in systemic lupus erythematosus.Frontiers in immunology · 2025Review
- Recent Advances of Type I Interferon on the Regulation of Immune Cells and the Treatment of Systemic Lupus Erythematosus.Journal of inflammation research · 2025Review
- Disentangling the riddle of systemic lupus erythematosus with antiphospholipid syndrome: blood transcriptome analysis reveals a less-pronounced IFN-signature and distinct molecular profiles in venous versus arterial events.Annals of the rheumatic diseases · 2024Article
- Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis.Kidney international reports · 2024Article
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
B cells orchestrate autoimmune responses in patients with systemic lupus erythematosus (SLE), but broad-based B cell-directed therapies show only modest efficacy while blunting humoral immune responses to vaccines and inducing immunosuppression. Development of more effective therapies targeting pathogenic clones is a currently unmet need. Here, we demonstrate enhanced activation of the ATR/Chk1 pathway of the DNA damage response (DDR) in B cells of patients with active SLE disease. Treatment of B cells with type I IFN, a key driver of immunity in SLE, induced expression of ATR via binding of interferon regulatory factor 1 to its gene promoter. Pharmacologic targeting of ATR in B cells, via a specific inhibitor (VE-822), attenuated their immunogenic profile, including proinflammatory cytokine secretion, plasmablast formation, and antibody production. Together, these findings identify the ATR-mediated DDR axis as the orchestrator of the type I IFN-mediated B cell responses in SLE and as a potential novel therapeutic target.
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