{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:05:03Z","timestamp":1789578303215,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T00:00:00Z","timestamp":1664064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Independent Research Fund Denmark","award":["4183-00198A"],"award-info":[{"award-number":["4183-00198A"]}]},{"name":"Independent Research Fund Denmark","award":["8020-00157B"],"award-info":[{"award-number":["8020-00157B"]}]},{"name":"Danish Multiple Sclerosis Society","award":["4183-00198A"],"award-info":[{"award-number":["4183-00198A"]}]},{"name":"Danish Multiple Sclerosis Society","award":["8020-00157B"],"award-info":[{"award-number":["8020-00157B"]}]},{"name":"Lundbeckfonden","award":["4183-00198A"],"award-info":[{"award-number":["4183-00198A"]}]},{"name":"Lundbeckfonden","award":["8020-00157B"],"award-info":[{"award-number":["8020-00157B"]}]},{"name":"The European Committee for Treatment and Research in Multiple Sclerosis","award":["4183-00198A"],"award-info":[{"award-number":["4183-00198A"]}]},{"name":"The European Committee for Treatment and Research in Multiple Sclerosis","award":["8020-00157B"],"award-info":[{"award-number":["8020-00157B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type I interferons (IFN), including IFN\u03b2, play a protective role in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Type I IFNs are induced by the stimulation of innate signaling, including via cytoplasmic RIG-I-like receptors. In the present study, we investigated the potential effect of a chimeric protein containing the key domain of RIG-I signaling in the production of CNS endogenous IFN\u03b2 and asked whether this would exert a therapeutic effect against EAE. We intrathecally administered an adeno-associated virus vector (AAV) encoding a fusion protein comprising RIG-I 2CARD domains (C) and the first 200 amino acids of mitochondrial antiviral-signaling protein (MAVS) (M) (AAV-CM). In vivo imaging in IFN\u03b2\/luciferase reporter mice revealed that a single intrathecal injection of AAV-CM resulted in dose-dependent and sustained IFN\u03b2 expression within the CNS. IFN\u03b2 expression was significantly increased for 7 days. Immunofluorescent staining in IFN\u03b2-YFP reporter mice revealed extraparenchymal CD45+ cells, choroid plexus, and astrocytes as sources of IFN\u03b2. Moreover, intrathecal administration of AAV-CM at the onset of EAE induced the suppression of EAE, which was IFN-I-dependent. These findings suggest that accessing the signaling pathway downstream of RIG-I represents a promising therapeutic strategy for inflammatory CNS diseases, such as MS.<\/jats:p>","DOI":"10.3390\/ijms231911292","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T23:13:27Z","timestamp":1664147607000},"page":"11292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting Signaling Pathway Downstream of RIG-I\/MAVS in the CNS Stimulates Production of Endogenous Type I IFN and Suppresses EAE"],"prefix":"10.3390","volume":"23","author":[{"given":"Anne K.","family":"Kronborg Hansen","sequence":"first","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4521-0410","authenticated-orcid":false,"given":"Magdalena","family":"Dubik","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Marczynska","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4919-6836","authenticated-orcid":false,"given":"Bhavya","family":"Ojha","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2458-8833","authenticated-orcid":false,"given":"Estanislao","family":"Nistal-Vill\u00e1n","sequence":"additional","affiliation":[{"name":"Microbiology Section, Department of Pharmaceutical and Health Science, Faculty of Pharmacy, University CEU San Pablo, Campus Montepr\u00edncipe, 28003 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-4562","authenticated-orcid":false,"given":"Gloria","family":"Gonz\u00e1lez Aseguinolaza","sequence":"additional","affiliation":[{"name":"Gene Therapy and Regulation of Gene Expression Program, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain"},{"name":"IdiSNA Navarra Institute for Health Research, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina S.","family":"Arengoth","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9315-6036","authenticated-orcid":false,"given":"Trevor","family":"Owens","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Khorooshi","sequence":"additional","affiliation":[{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/glia.22608","article-title":"Interferons in the Central Nervous System: A Few Instruments Play Many Tunes: Glial Interferons","volume":"62","author":"Owens","year":"2014","journal-title":"Glia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.expneurol.2014.01.001","article-title":"Pattern Recognition Receptors and Central Nervous System Repair","volume":"258","author":"Kigerl","year":"2014","journal-title":"Exp. 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