{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:06:59Z","timestamp":1789020419363,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Optic neuritis (ON) is a neuroinflammatory autoimmune disease harboring autoreactive lymphocytes. Effector memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells (CD4\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>em<\/jats:sub>\n                    ) represent a prominently expanded and pro\u2010inflammatory subset within this compartment, yet their pathogenic metabolic programs remain poorly defined. B cell dysfunction also contributes to ON pathogenesis. However, whether T cell\u2010intrinsic metabolic rewiring directly fuels this B cell dysregulation awaits elucidation. Here, through single\u2010cell transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from ON patients, we conceptualized a pathological circuit linking T cell metabolic reprogramming to aberrant T\u2010B crosstalk. In pathogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>em<\/jats:sub>\n                    , JAK1 upregulation and enhanced STAT3 phosphorylation propagated a metabolic rewiring transcriptional program and secured T cell fitness via MCL1 induction. An inferred cholesterol export signature distinguished this subset and engaged the nuclear sensor RORA on B cells to instruct pro\u2010inflammatory polarization and humoral commitment. In turn, subverted B cells perpetuated exaggerated antigen presentation and cytokine secretion, cementing pathogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>em<\/jats:sub>\n                    differentiation and sustaining a self\u2010amplifying inflammatory loop. Cross\u2010disease profiling extended this axis to allied autoimmune disorders. Selective JAK1 blockade with upadacitinib (UPA) restored immune homeostasis and attenuated experimental autoimmune encephalomyelitis (EAE), phenocopied by MCL1 inhibition. Together, these findings nominate UPA as a targeted therapy for ON and allied autoimmune disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.77701","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:31:08Z","timestamp":1789018268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Upadacitinib Restrains the Pathogenic Fitness of CD4\n                    <sup>+<\/sup>\n                    T Cells and Aberrant B Cell Programming in Optic Neuritis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9190-1145","authenticated-orcid":false,"given":"Gengchen","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"State Key Laboratory of Eye Health Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"State Key Laboratory of Eye Health Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Han","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Bengbu Medical University Bengbu Medical University  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine Qinghai University  Xining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"State Key Laboratory of Eye Health Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Bengbu Medical University Bengbu Medical University  Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7359-6816","authenticated-orcid":false,"given":"Hao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"State Key Laboratory of Eye Health Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"The First Affiliated Hospital of Bengbu Medical University Bengbu Medical University  Bengbu China"},{"name":"Department of Ophthalmology Zhuzhou Hospital Affiliated to Xiangya School of Medicine Central South University  Zhuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science Sun Yat\u2010sen University Guangdong Provincial Clinical Research Center for Ocular Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"State Key Laboratory of Eye Health Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-4711","authenticated-orcid":false,"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science Sun Yat\u2010sen University Guangdong Provincial Clinical Research Center for Ocular Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8917-0417","authenticated-orcid":false,"given":"Wenjun","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Wuxi No.2 People's Hospital Jiangnan University Medical Center  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohuai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"State Key Laboratory of Eye Health Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science Sun Yat\u2010sen University Guangdong Provincial Clinical Research Center for Ocular Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0506-6362","authenticated-orcid":false,"given":"Wenru","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"State Key Laboratory of Eye Health Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(22)00200\u20109"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNO.0000000000002031"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0b013e328358b202"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201073792\u2010z"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2025.12.003"},{"issue":"6","key":"e_1_2_11_7_1","first-page":"727","article-title":"Multiple Sclerosis Risk After Optic Neuritis: Final Optic Neuritis Treatment Trial Follow\u2010Up","volume":"65","year":"2008","journal-title":"Archives of Neurology"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108580"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010025\u201003424\u20104"},{"issue":"1","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.imlet.2004.07.017","article-title":"New Insights Into Cell Responses Involved in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis","volume":"96","author":"El Behi M.","year":"2005","journal-title":"Immunology Letters"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000330242"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010024\u201001148\u20108"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010023\u201001733\u20105"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13024"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abk2132"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010789"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2413449"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2021.3023"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2008250"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(22)00581\u20105"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1110765"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.07.026"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2025.03.013"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adh0368"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.55"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201016904\u20103"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010021\u201001033\u2010z"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010immunol\u2010032712\u2010095956"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584\u2010019\u20100356\u2010x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl9467"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010024\u201001804\u20101"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010023\u201001938\u20104"},{"issue":"10","key":"e_1_2_11_33_1","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20190613","article-title":"PKM2 Promotes Th17 Cell Differentiation and Autoimmune Inflammation by Fine\u2010Tuning STAT3 Activation","volume":"217","author":"Damasceno L. E. A.","year":"2020","journal-title":"Journal of Experimental Medicine"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010021\u201001214\u2010y"},{"issue":"12","key":"e_1_2_11_35_1","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.neo.2021.10.003","article-title":"STAT3 as a Mediator of Oncogenic Cellular Metabolism: Pathogenic and Therapeutic Implications","volume":"23","author":"To\u0161i\u0107 I.","year":"2021","journal-title":"Neoplasia"},{"issue":"7","key":"e_1_2_11_36_1","doi-asserted-by":"crossref","DOI":"10.1172\/JCI153247","article-title":"IL\u20109\/STAT3\/Fatty Acid Oxidation\u2010Mediated Lipid Peroxidation Contributes to Tc9 Cell Longevity and Enhanced Antitumor Activity","volume":"132","author":"Xiao L.","year":"2022","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.10.013"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.11.001"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013201"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02067"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.02.042"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2024.153740"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3538"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.03.010"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010022\u201001376\u2010y"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2026.01.015"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.07.033"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.05.025"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102799\u20102"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri726"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adw1836"},{"issue":"11","key":"e_1_2_11_52_1","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1002\/art.41032","article-title":"Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double\u2010Blind, Randomized Controlled Trial","volume":"71","author":"Fleischmann R.","year":"2019","journal-title":"Arthritis and Rheumatology"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022516"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212728"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010025\u201003328\u2010y"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010019\u201000855\u20100"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.19391"},{"key":"e_1_2_11_58_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18502\/jovr.v20.14952","article-title":"Successful Use of Upadacitinib, a Selective JAK Inhibitor, in the Treatment of Two Cases of Recalcitrant Chronic Uveitis","volume":"20","author":"Dominguez D.","year":"2025","journal-title":"Journal of Ophthalmic and Vision Research"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.285"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9437"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010019\u20100619\u20100"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009234\u20106"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021246\u20109"},{"issue":"12","key":"e_1_2_11_64_1","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1038\/s41596-024-01137-1","article-title":"CellPhoneDB v5: Inferring Cell\u2010Cell Communication From Single\u2010Cell Multiomics Data","volume":"20","author":"Troul\u00e9 K.","year":"2025","journal-title":"Nature Protocols"},{"key":"e_1_2_11_65_1","doi-asserted-by":"crossref","unstructured":"J. A. Bibby H. A. Purvis T. Hayday A. Chandra K. Okkenhaug S. Rosenzweig I. Aksentijevich M. Wood H. J. Lachmann C. Kemper A. P. Cope E. Perucha Cholesterol metabolism drives regulatory B cell IL\u201010 through provision of geranylgeranyl pyrophosphate. Nat Commun 11 3412 (2020).","DOI":"10.1038\/s41467-020-17179-4"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77701","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77701","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77701","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:31:11Z","timestamp":1789018271000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":64,"alternative-id":["10.1002\/advs.77701"],"URL":"https:\/\/doi.org\/10.1002\/advs.77701","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"assertion":[{"value":"2026-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77701"}}