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Prior attempts to treat NMOSD with interferon\u2010beta (IFN\u2010\u03b2), a disease\u2010modifying therapy for multiple sclerosis, resulted in worsening of disease activity, with an unknown mechanism. Here, robust activation of the cGAS\u2010STING\u2010IFN\u2010I signaling pathway is identified\u00a0in myeloid cells in both the periphery and central nervous system. The abnormal IFN\u2010I response gives rise to an increase in the number of AQP4 antigen\u2010specific autoreactive T cells.\n                    <jats:italic>Sting<\/jats:italic>\n                    deficiency can significantly blunt the activation of AQP4\u2010specific T cells, as well as the IFN\u2010I activity in microglia, and attenuate astrocyte damage. Consequently, the clinical manifestation of NMOSD is ameliorated in a passive transfer mouse model of NMOSD. Further, treatment with STING inhibitor H151 alleviates the severity of NMOSD mouse models. These findings uncover the cGAS\u2010STING\u2010IFN\u2010I pathway in promoting autoreactive T cells and establish a foundation for inhibiting this pathway as a new therapeutic revenue for NMOSD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500942","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T08:50:07Z","timestamp":1753087807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Type I Interferon Signaling Augments Autoimmunity in Neuromyelitis Optica Spectrum Disorder"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9957-9478","authenticated-orcid":false,"given":"Tian\u2010Xiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology Tianjin Medical University General Hospital Tianjin 300052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics School of Basic Medical Sciences Tianjin Medical University Tianjin 300070 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8802-0114","authenticated-orcid":false,"given":"Xue","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Medical University General Hospital Tianjin 300052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Medical University General Hospital Tianjin 300052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuegan","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Soochow University Changzhou Jiangsu 213003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naiyuan","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The Third Affiliated Hospital of Soochow University Changzhou Jiangsu 213003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Medical University General Hospital Tianjin 300052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenning","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Medical University General Hospital Tianjin 300052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Neurology Tianjin Medical University General Hospital Tianjin 300052 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander Y. 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