{"doi":"10.1101/2024.01.23.576771","title":"Epidermal ZBP1 stabilizes mitochondrial Z-DNA to drive UV-induced IFN signaling in autoimmune photosensitivity","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. Here, 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 significantly upregulated in the epidermis of adult and pediatric patients with autoimmune photosensitivity. Strikingly, lupus keratinocytes accumulate extensive cytosolic Z-DNA after UVB, and transfection of keratinocytes with Z-DNA results in stronger IFN production through cGAS-STING activation compared to B-DNA. ZBP1 knockdown abrogates UV-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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485012,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":692228,"name":"Mack B. Reynolds","orcid":"0000-0002-8445-3749","position":1,"is_corresponding":false},{"id":1327641,"name":"Bin Xu","orcid":"0000-0001-7429-3908","position":2,"is_corresponding":false},{"id":353207,"name":"Mehrnaz Gharaee‐Kermani","orcid":"0000-0002-2177-2427","position":3,"is_corresponding":false},{"id":1328080,"name":"Yiqing Gao","orcid":null,"position":4,"is_corresponding":false},{"id":249277,"name":"Céline C. Berthier","orcid":"0000-0003-3539-1075","position":5,"is_corresponding":false},{"id":1327642,"name":"Svenja Henning","orcid":"0000-0002-7895-6729","position":6,"is_corresponding":false},{"id":926773,"name":"Shannon Loftus","orcid":"0000-0003-0608-5255","position":7,"is_corresponding":false},{"id":851382,"name":"Kelsey E. McNeely","orcid":"0000-0002-8255-6816","position":8,"is_corresponding":false},{"id":406738,"name":"Amanda Victory","orcid":"0000-0002-4948-5702","position":9,"is_corresponding":false},{"id":652104,"name":"Craig J. Dobry","orcid":"0000-0002-1468-1156","position":10,"is_corresponding":false},{"id":353208,"name":"Grace A. Hile","orcid":"0000-0002-3629-8633","position":11,"is_corresponding":false},{"id":236682,"name":"Feiyang Ma","orcid":"0000-0002-6260-0787","position":12,"is_corresponding":false},{"id":479545,"name":"Jessica L. Turnier","orcid":"0000-0002-1127-7879","position":13,"is_corresponding":false},{"id":12829,"name":"Jóhann E. Guðjónsson","orcid":"0000-0002-0080-0812","position":14,"is_corresponding":false},{"id":564237,"name":"Mary O’Riordan","orcid":"0000-0001-6014-4637","position":15,"is_corresponding":false},{"id":233184,"name":"J. Michelle Kahlenberg","orcid":"0000-0002-4006-8945","position":16,"is_corresponding":false},{"id":323210,"name":"Benjamin Klein","orcid":"0000-0002-3412-5536","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:07:47.633574Z","pmid":"38328232","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}