{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T23:52:47Z","timestamp":1779148367812,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI137047"],"award-info":[{"award-number":["R01AI137047"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY027346"],"award-info":[{"award-number":["R01EY027346"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG-1602-07722"],"award-info":[{"award-number":["RG-1602-07722"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Interferon (IFN)-\u03b2 is a popular therapy for multiple sclerosis (MS). However, 25\u201340% of patients are nonresponsive to this therapy, and it worsens neuromyelitis optica (NMO), another neuroinflammatory disease. We previously identified, in both NMO patients and in mice, that IFN-\u03b2 treatment had inflammatory effects in T Helper (TH) 17-induced disease through the production of the inflammatory cytokine IL-6. However, other studies have shown that IFN-\u03b2 inhibits the differentiation and function of TH17 cells. In this manuscript, we identified that IFN-\u03b2 had differential effects on discrete stages of TH17 development. During early TH17 development, IFN-\u03b2 inhibits IL-17 production. Conversely, during late TH17 differentiation, IFN-\u03b2 synergizes with IL-23 to promote a pathogenic T cell that has both TH1 and TH17 characteristics and expresses elevated levels of the potent inflammatory cytokines IL-6 and GM-CSF and the transcription factor BLIMP. Together, these findings help resolve a paradox surrounding IFN-\u03b2 and TH17-induced disease and illuminate the pathways responsible for the pathophysiology of NMO and MS patients who are IFN-\u03b2 nonresponders.<\/jats:p>","DOI":"10.3390\/cells10082139","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T08:44:45Z","timestamp":1629449085000},"page":"2139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Interferon-\u03b2 Intensifies Interleukin-23-Driven Pathogenicity of T Helper Cells in Neuroinflammatory Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Agnieshka","family":"Agasing","sequence":"first","affiliation":[{"name":"Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L.","family":"Quinn","sequence":"additional","affiliation":[{"name":"Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5464-6518","authenticated-orcid":false,"given":"Gaurav","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Axtell","sequence":"additional","affiliation":[{"name":"Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ana.10290","article-title":"Assessment of different treatment failure criteria in a cohort of relapsing-remitting multiple sclerosis patients treated with interferon beta: Implications for clinical trials","volume":"52","author":"Rio","year":"2002","journal-title":"Ann. 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