{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:55:47Z","timestamp":1785941747390,"version":"3.56.0"},"reference-count":66,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100028938","name":"Teshinsky Family Foundation","doi-asserted-by":"crossref","award":["Gift"],"award-info":[{"award-number":["Gift"]}],"id":[{"id":"10.13039\/100028938","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"crossref","award":["US-PEG-14-10648"],"award-info":[{"award-number":["US-PEG-14-10648"]}],"id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Interferon &amp; Cytokine Research"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    Multiple sclerosis (MS) is a central nervous system (CNS) disease with autoimmune inflammation, demyelination, and neurodegeneration. Untreated MS patients exhibit subnormal activation of the p-Ser-STAT1 transcription factor in peripheral blood mononuclear cells (PBMCs), causing weak interferon (IFN) signaling and low expression of some IFN-stimulated genes (ISGs). IFN-\u03b2 therapy reduces MS exacerbations, delays progression, and largely corrects abnormal gene expression in PBMC. We hypothesize that long-term IFN-\u03b2 therapy improves weak IFN responses and regulates MS immunity through a priming effect and induction of a more IFN-responsive state. The duration and strength of IFN-stimulated gene expression during prolonged therapy and their diminution after discontinuation are unknown. Using paired comparisons of 1- and 7-month PEG-IFN-\u03b2-treated MS patients\u2019 PBMCs, we investigated short- and long-term responses to\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    IFN-\u03b2. Prolonged therapy created a new IFN setpoint with elevated expression of antiviral, immune, anti-inflammatory, and neuroprotective ISG while decreasing inflammatory and metabolic gene expression, often doubling their half-life. Genes that inhibit IFN-\u03b2 signaling also showed long-term induction, reflecting a regulatory state that prevents overactivation. Strong IFN responses during long-term therapy of MS reflect a shift from subnormal IFN signaling and dysregulated immune control to a more responsive state that persists for months.\n                  <\/jats:p>","DOI":"10.1177\/10799907261458149","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T13:50:26Z","timestamp":1781099426000},"page":"253-263","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-Term IFN-\u03b2 Therapy Enhances and Prolongs IFN Responses in Multiple Sclerosis"],"prefix":"10.1177","volume":"46","author":[{"given":"Jeffrey","family":"Ke","sequence":"first","affiliation":[{"name":"Neurology MC-2030 J-218, University of Chicago Medicine, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conrad","family":"Moss","sequence":"additional","affiliation":[{"name":"Neurology MC-2030 J-218, University of Chicago Medicine, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Neurology MC-2030 J-218, University of Chicago Medicine, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6423-1495","authenticated-orcid":false,"given":"Anthony T.","family":"Reder","sequence":"additional","affiliation":[{"name":"Neurology MC-2030 J-218, University of Chicago Medicine, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-020-00590-7"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20180250"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21187"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70068-7"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1987.tb03550.x"},{"issue":"5","key":"e_1_3_4_8_1","first-page":"1142","article-title":"Hepatic metallothionein in patients with chronic hepatitis C: Relationship with severity of liver disease and response to treatment","volume":"98","author":"Carrera G","year":"2003","unstructured":"Carrera G, , Paternain JL, , Carrere N, et al. Hepatic metallothionein in patients with chronic hepatitis C: Relationship with severity of liver disease and response to treatment. Am J Gastroenterol 2003;98(5):1142\u20131149.","journal-title":"Am J Gastroenterol"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.611795"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700720"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp228"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.MR0718-261RR"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm863"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.739918"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01159-19"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)03334-0"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00182-0"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.09.059"},{"key":"e_1_3_4_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000622"},{"key":"e_1_3_4_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182143577"},{"key":"e_1_3_4_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2024.578328"},{"key":"e_1_3_4_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1245622"},{"key":"e_1_3_4_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0007"},{"key":"e_1_3_4_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1029223"},{"key":"e_1_3_4_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182535cf6"},{"key":"e_1_3_4_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-54"},{"key":"e_1_3_4_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514561909"},{"key":"e_1_3_4_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458509352794"},{"key":"e_1_3_4_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143393"},{"key":"e_1_3_4_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.84"},{"key":"e_1_3_4_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(06)91007-4"},{"key":"e_1_3_4_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.256370"},{"key":"e_1_3_4_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.10.006"},{"key":"e_1_3_4_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0330867"},{"key":"e_1_3_4_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.2581"},{"key":"e_1_3_4_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12050520"},{"key":"e_1_3_4_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-3819-y"},{"key":"e_1_3_4_38_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2022.0238"},{"key":"e_1_3_4_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00910.x"},{"key":"e_1_3_4_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513507819"},{"key":"e_1_3_4_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/biof.44"},{"key":"e_1_3_4_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3021-z"},{"key":"e_1_3_4_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000847"},{"key":"e_1_3_4_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00281"},{"key":"e_1_3_4_45_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2013.0158"},{"key":"e_1_3_4_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.70268"},{"key":"e_1_3_4_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.001417621152067"},{"key":"e_1_3_4_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.035"},{"key":"e_1_3_4_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.634937"},{"key":"e_1_3_4_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14181445"},{"key":"e_1_3_4_51_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.23921"},{"key":"e_1_3_4_52_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-092818-015756"},{"key":"e_1_3_4_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02716.x"},{"key":"e_1_3_4_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(85)92801-6"},{"key":"e_1_3_4_55_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306847"},{"key":"e_1_3_4_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2003.tb01455.x"},{"key":"e_1_3_4_57_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.4.655"},{"key":"e_1_3_4_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158077"},{"key":"e_1_3_4_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1105309"},{"key":"e_1_3_4_60_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1176177"},{"key":"e_1_3_4_61_1","doi-asserted-by":"publisher","DOI":"10.1097\/BS9.0000000000000212"},{"key":"e_1_3_4_62_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.6.2093"},{"key":"e_1_3_4_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00381-6"},{"key":"e_1_3_4_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"e_1_3_4_65_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01557-22"},{"key":"e_1_3_4_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2021.07.003"},{"key":"e_1_3_4_67_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01509-25"}],"container-title":["Journal of Interferon &amp; Cytokine Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10799907261458149","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10799907261458149","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10799907261458149","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:18:23Z","timestamp":1785939503000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10799907261458149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":66,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9,1]]}},"alternative-id":["10.1177\/10799907261458149"],"URL":"https:\/\/doi.org\/10.1177\/10799907261458149","relation":{},"ISSN":["1079-9907","1557-7465"],"issn-type":[{"value":"1079-9907","type":"print"},{"value":"1557-7465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]}}}