{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T07:53:33Z","timestamp":1775202813348,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA229254"],"award-info":[{"award-number":["R01CA229254"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR077194"],"award-info":[{"award-number":["R01AR077194"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)\u2013IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV\u2013IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10\u2013null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV\u2013IL-27. Our study revealed a major role for IL-10 in AAV\u2013IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.2400056","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:33:59Z","timestamp":1720442039000},"page":"559-566","source":"Crossref","is-referenced-by-count":3,"title":["IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10"],"prefix":"10.1093","volume":"213","author":[{"given":"Jin-Qing","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, The Ohio State University , Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Jabbari","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, University of Iowa , Iowa City, IA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-904X","authenticated-orcid":false,"given":"Cho-Hao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, The Ohio State University , Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venu","family":"Akkanapally","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, The Ohio State University , Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy L","family":"Frankel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, The Ohio State University , Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8272-0807","authenticated-orcid":false,"given":"Sujit","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, The Ohio State University , Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"He","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine and Comprehensive Cancer Center, The Ohio State University , Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan","family":"Zheng","sequence":"additional","affiliation":[{"name":"OncoC4 , Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"OncoC4 , Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9476-8376","authenticated-orcid":false,"given":"Xue-Feng","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Comprehensive Cancer Center, The Ohio State University , Columbus, OH"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"2025012305141154200_r1","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"2025012305141154200_r2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/83784","article-title":"Disruption of a new forkhead\/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse","volume":"27","author":"Brunkow","year":"2001","journal-title":"Nat. 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