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Here, we show that Tregs from ITP patients undergo a profound shift in subset composition and transcriptional states, with expansion of ANXA1\n                    <jats:sup>high<\/jats:sup>\n                    and IKZF2\n                    <jats:sup>high<\/jats:sup>\n                    populations and aberrant interferon signaling. Single-cell transcriptomic and functional analyses revealed that in normal controls, immature-like Tregs predominantly exhibit a FOXP3\n                    <jats:sup>high<\/jats:sup>\n                    \/CCR6\n                    <jats:sup>high<\/jats:sup>\n                    phenotype, whereas in chronic ITP they adopt an ANXA1\n                    <jats:sup>high<\/jats:sup>\n                    state enriched for interferon-stimulated gene (ISG)\n                    <jats:sup>high<\/jats:sup>\n                    subclusters. Elevated ISG scores in chronic ITP Tregs mark a pathological transition, with RSAD2 (Viperin) emerging as a key regulator. Viperin overexpression impaired Treg suppressive function and promoted Th1-skewed activation in conventional T cells. Mechanistically, ELF1 directly binds the RSAD2 promoter and activates its transcription via increased H3K4Me3 deposition. These findings identify the ELF1-Viperin axis as the driver of Treg dysfunction in ITP and a potential target for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1186\/s12964-025-02511-6","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T07:00:15Z","timestamp":1763622015000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interferon-stimulated Viperin impairs Treg function in autoimmune thrombocytopenia"],"prefix":"10.1186","volume":"23","author":[{"given":"Tengda","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifa","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"2511_CR1","doi-asserted-by":"crossref","unstructured":"Al-Samkari H. 2025 update on clinical trials in immune thrombocytopenia. 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The results were assessed blindly for all the experiments using clinical samples to ensure scientific rigor. All procedures in this study were approved by the Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (clinical trial number 2024-K-224-01).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"500"}}