ArticleScience immunology2025
Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity.
Article in Science immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- Mechanical stress-mediated ferritinophagy aggravates cartilage endplate degeneration via a PIEZO1-NCOA4-ZBP1 axis.Autophagy · 2026Article
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Myeloid infiltration and epidermal dysregulation characterize cutaneous photosensitivity in systemic lupus erythematosus.Science translational medicine · 2026Article
- Single-cell and spatial transcriptomics implicate vascular cell orchestration of inflammatory changes after UV light exposure in skin.The Journal of investigative dermatology · 2026Article
- Mucosal-associated invariant T cells support IL-15-dependent Treg response in skin injury and promote resolution of skin inflammation.bioRxiv : the preprint server for biology · 2026Article
- Mitochondria as convergence hubs for innate immunity pathways.Communications biology · 2026Review
- Z-nucleic acid-mediated PANoptosis in infection, inflammation, and cancer.Communications biology · 2026Review
- Integrative Analyses Identify a cGAS-STING Pathway-Driven Signature With Context-Dependent Roles in Systemic Lupus Erythematosus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cryo-EM structures of anti Z-DNA antibodies in complex with antigen reveal distinct recognition modes of a left-handed geometry.Nucleic acids research · 2026Article
- ZBP1 mediated restriction of Toxoplasma gondii in both the early acute and chronic brain stages of infection.ImmunoHorizons · 2026Article
- Upregulated ZBP1 Is Associated with B-Cell Dysregulation in Systemic Lupus Erythematosus.Biomedicines · 2026Article
- A MIF-p38-GSDMD inflammatory loop in keratinocytes underlies UVB-induced cutaneous lupus.Cell death & disease · 2026Article
- Formation and biological implications of Z-DNA.Trends in genetics : TIG · 2026Review
- Stress-induced sympathetic hyperactivation drives hair follicle necrosis to trigger autoimmunity.Cell · 2026Article
- Unravelling the noncanonical extracellular DNA structures in biofilm and NETosis.Nucleic acids research · 2026Review
- Neutrophil extracellular traps prime the ZBP1-cGAS sensor complex, triggering necroptosis and inflammatory injury in acute pancreatitis.International journal of biological sciences · 2026Article
- IFI204-STING drives protective innate immunity against gangrenousFrontiers in immunology · 2026Article
- Epidermal Interferon-κ Drives Cutaneous Lupus-Like Lesions, Photosensitivity, and Systemic Autoimmunity In Vivo.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Dermatomyositis is characterized by JAK1-mediated monocyte-driven vasculopathy and inflammation.Science translational medicine · 2025Article
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Abstract
Photosensitivity is observed in numerous autoimmune diseases and drives poor quality of life and disease flares. Elevated epidermal type I interferon (IFN) production primes for photosensitivity and enhanced inflammation, but the substrates that sustain and amplify this cycle remain undefined. We show that IFN-induced Z-DNA binding protein 1 (ZBP1) stabilizes ultraviolet (UV) B-induced cytosolic Z-DNA derived from oxidized mitochondrial DNA. ZBP1 is up-regulated in the epidermis of adult and pediatric patients with autoimmune photosensitivity. In patient-derived samples, lupus keratinocytes accumulate extensive cytosolic Z-DNA after UVB exposure, and transfection of keratinocytes with Z-DNA results in stronger IFN production through cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) activation compared with the more conventional B-DNA. ZBP1 knockdown abrogates UVB-induced IFN responses, whereas overexpression results in a lupus-like phenotype with spontaneous Z-DNA accumulation and IFN production. Our results highlight Z-DNA and ZBP1 as critical mediators for UVB-induced inflammation and uncover how type I IFNs prime for cutaneous inflammation in photosensitivity.
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