{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:21:10Z","timestamp":1762431670010,"version":"3.38.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multiple sclerosis (MS) is a chronic autoimmune disease with no curative treatment. The immune regulatory properties of type I IFNs have led to the approval of IFN-\u03b2 for the treatment of relapsing-remitting MS. However, there is still an unmet need to improve the tolerability and efficacy of this therapy. In this work, we evaluated the sustained delivery of IFN-\u03b11, either alone or fused to apolipoprotein A-1 by means of an adeno-associated viral (AAV) system in the mouse model of myelin oligodendrocyte glycoprotein\u2013induced experimental autoimmune encephalomyelitis. These in vivo experiments demonstrated the prophylactic and therapeutic efficacy of the AAV\u2013IFN-\u03b1 or AAV\u2013IFN-\u03b1 fused to apolipoprotein A-1 vectors in experimental autoimmune encephalomyelitis, even at low doses devoid of hematological or neurologic toxicity. The sustained delivery of such low-dose IFN-\u03b1 resulted in immunomodulatory effects, consisting of proinflammatory monocyte and T regulatory cell expansion. Moreover, encephalitogenic T lymphocytes from IFN-\u03b1\u2013treated mice re-exposed to the myelin oligodendrocyte glycoprotein peptide in vitro showed a reduced proliferative response and cytokine (IL-17A and IFN-\u03b3) production, in addition to upregulation of immunosuppressive molecules, such as IL-10, IDO, or PD-1. In conclusion, the results of the present work support the potential of sustained delivery of low-dose IFN-\u03b1 for the treatment of MS and likely other T cell\u2013dependent chronic autoimmune disorders.<\/jats:p>","DOI":"10.4049\/jimmunol.1801462","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T20:25:14Z","timestamp":1560803114000},"page":"696-704","source":"Crossref","is-referenced-by-count":9,"title":["Treatment of Experimental Autoimmune Encephalomyelitis by Sustained Delivery of Low-Dose IFN-\u03b1"],"prefix":"10.1093","volume":"203","author":[{"given":"Marcos","family":"Vasquez","sequence":"first","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 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,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aitor","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4034-2796","authenticated-orcid":false,"given":"Shirley","family":"Tenesaca","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2119-3967","authenticated-orcid":false,"given":"Myriam","family":"Fernandez-Sendin","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Gomar","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-553X","authenticated-orcid":false,"given":"Nuria","family":"Ardaiz","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia Augusta","family":"Di Trani","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Casares","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-3881","authenticated-orcid":false,"given":"Juan Jose","family":"Lasarte","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1119-4368","authenticated-orcid":false,"given":"Francisco","family":"Lozano","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e9diques August Pi i Sunyer , Barcelona 08036 ,","place":["Spain"]},{"name":"Servei d\u2019Immunologia, Hospital Cl\u00ednic de Barcelona , Barcelona 08036 ,","place":["Spain"]},{"name":"Departament de Biomedicina, Universitat de Barcelona , Barcelona 08007 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-1865","authenticated-orcid":false,"given":"Pedro","family":"Berraondo","sequence":"additional","affiliation":[{"name":"Program of Immunology and Immunotherapy, Cima University of Navarra , Pamplona 31008 ,","place":["Spain"]},{"name":"Navarra Institute for Health Research , Pamplona 31008 ,","place":["Spain"]},{"name":"Centro de 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