{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:14:54Z","timestamp":1772118894526,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["5R01NS107523"],"award-info":[{"award-number":["5R01NS107523"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1TR001431"],"award-info":[{"award-number":["TL1TR001431"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["JF\u20101806\u201031381"],"award-info":[{"award-number":["JF\u20101806\u201031381"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Multiple sclerosis (MS) is a chronic inflammatory disease characterized by immune\u2010mediated demyelination of the central nervous system, resulting in extensive neurological deficit and remyelination impairment. We have previously found that interleukin\u2010four induced one (IL4I1) protein modulates CNS inflammation and enhances remyelination in mouse models of experimental demyelination. However, it remained unclear if IL4I1 regulates lymphocyte activity in MS. To assess the therapeutic potential of IL4I1 in MS, we investigated the impact of IL4I1 treatment on human lymphocytes from peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and MS patients. We found that IL4I1 increased the relative densities of Th2 and regulatory T\u2010cells, while reducing Th17 cell density in healthy control (HC) samples. Furthermore, IL4I1\u2010treated lymphocytes promoted CNS remyelination when grafted into demyelinated spinal cord lesions in mice. We found that baseline endogenous\n                    <jats:italic>IL4I1<\/jats:italic>\n                    expression was reduced in people with MS. However, unlike HCs, IL4I1 treatment had no significant effect on\n                    <jats:italic>IL17<\/jats:italic>\n                    or\n                    <jats:italic>TOB1<\/jats:italic>\n                    expression in lymphocytes derived from MS patients. These results suggest that IL4I1 skews CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cells to a regulatory state in healthy human lymphocytes, which may be essential for promoting remyelination. However, IL4I1 appears unable to exert its influence on lymphocytes in MS, indicating that impaired IL4I1\u2010mediated activity may underlie MS pathology.\n                  <\/jats:p>","DOI":"10.1002\/prp2.70062","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T23:03:46Z","timestamp":1742339026000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Effects of\n                    <scp>IL4I1<\/scp>\n                    Protein on Lymphocytes From Healthy and Multiple Sclerosis Patients"],"prefix":"10.1002","volume":"13","author":[{"given":"Stephanie E.","family":"Davis","sequence":"first","affiliation":[{"name":"Department of Biology Georgetown University  Washington DC USA"},{"name":"Interdisciplinary Program in Neuroscience Georgetown University  Washington DC USA"},{"name":"Georgetown University School of Medicine Georgetown University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biology Georgetown University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia E.","family":"Nanescu","sequence":"additional","affiliation":[{"name":"Department of Biology Georgetown University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahesh N.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biology Georgetown University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryna","family":"Baydyuk","sequence":"additional","affiliation":[{"name":"Department of Biology Georgetown University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helena C.","family":"Oft","sequence":"additional","affiliation":[{"name":"Department of Biology Georgetown University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faria S.","family":"Amjad","sequence":"additional","affiliation":[{"name":"Department of Neurology MedStar Georgetown University Hospital  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Wellstein","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program in Neuroscience Georgetown University  Washington DC USA"},{"name":"Lombardi Cancer Center Georgetown University Medical Center  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0996-9451","authenticated-orcid":false,"given":"Jeffrey K.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biology Georgetown University  Washington DC USA"},{"name":"Interdisciplinary Program in Neuroscience Georgetown University  Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000094"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08220-X"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1401483"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.09.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.200"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015910792246218"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn917"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61620-7"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142979"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.380"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww254"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.17.9979"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(02)00295-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344047"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805065105"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22366"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000560"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1444"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.12.013"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx008"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01191213"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445000"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041119"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4528"},{"key":"e_1_2_10_26_1","first-page":"1","article-title":"Myeloid Cell\u2010Associated Aromatic Amino Acid Metabolism Facilitates CNS Myelin Regeneration","volume":"9","author":"Hu J.","year":"2024","journal-title":"Nature Partner Journals Regenerative Medicine"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701734"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T04:23:48Z","timestamp":1744777428000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.70062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/prp2.70062"],"URL":"https:\/\/doi.org\/10.1002\/prp2.70062","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.09.17.558132","asserted-by":"object"}]},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]},"assertion":[{"value":"2024-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70062"}}