{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:41:00Z","timestamp":1779183660238,"version":"3.51.4"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T00:00:00Z","timestamp":1624838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100007366","name":"Fondazione Italiana Sclerosi Multipla","doi-asserted-by":"publisher","award":["FISM2013\/R\/13"],"award-info":[{"award-number":["FISM2013\/R\/13"]}],"id":[{"id":"10.13039\/100007366","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1007\/s12035-021-02465-z","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T10:03:10Z","timestamp":1624874590000},"page":"4816-4827","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Transcriptomic Analysis of Peripheral Monocytes upon Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients"],"prefix":"10.1007","volume":"58","author":[{"given":"G.","family":"Sferruzza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Clarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Mascia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Ferr\u00e8","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Ottoboni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Sorosina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Moiola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Martinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Comi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Martinelli Boneschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Filippi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Provero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2550-0805","authenticated-orcid":false,"given":"Federica","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,28]]},"reference":[{"key":"2465_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s41572-018-0041-4","volume":"4","author":"M Filippi","year":"2018","unstructured":"Filippi M, Bar-Or A, Piehl F et al (2018) Multiple sclerosis. Nat Rev Dis Prim 4:43. https:\/\/doi.org\/10.1038\/s41572-018-0041-4","journal-title":"Nat Rev Dis Prim"},{"key":"2465_CR2","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","volume":"372","author":"A Compston","year":"2008","unstructured":"Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502\u20131517. https:\/\/doi.org\/10.1016\/S0140-6736(08)61620-7","journal-title":"Lancet"},{"key":"2465_CR3","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/nrneurol.2016.110","volume":"12","author":"MK Mishra","year":"2016","unstructured":"Mishra MK, Yong VW (2016) Myeloid cells \u2014 targets of medication in multiple sclerosis. Nat Rev Neurol 12:539\u2013551. https:\/\/doi.org\/10.1038\/nrneurol.2016.110","journal-title":"Nat Rev Neurol"},{"key":"2465_CR4","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1084\/jem.20170355","volume":"214","author":"AA Patel","year":"2017","unstructured":"Patel AA, Zhang Y, Fullerton JN et al (2017) The fate and lifespan of human monocyte subsets in steady state and systemic inflammation. J Exp Med 214:1913\u20131923. https:\/\/doi.org\/10.1084\/jem.20170355","journal-title":"J Exp Med"},{"key":"2465_CR5","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nri.2017.28","volume":"17","author":"CV Jakubzick","year":"2017","unstructured":"Jakubzick CV, Randolph GJ, Henson PM (2017) Monocyte differentiation and antigen-presenting functions. Nat Rev Immunol 17:349\u2013362. https:\/\/doi.org\/10.1038\/nri.2017.28","journal-title":"Nat Rev Immunol"},{"key":"2465_CR6","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/400_2009_22","volume":"51","author":"C Stoeckle","year":"2010","unstructured":"Stoeckle C, Tolosa E (2010) Antigen processing and presentation in multiple sclerosis. Results Probl Cell Differ 51:149\u2013172. https:\/\/doi.org\/10.1007\/400_2009_22","journal-title":"Results Probl Cell Differ"},{"key":"2465_CR7","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/nn.2887","volume":"14","author":"B Ajami","year":"2011","unstructured":"Ajami B, Bennett JL, Krieger C et al (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci 14:1142\u20131149. https:\/\/doi.org\/10.1038\/nn.2887","journal-title":"Nat Neurosci"},{"key":"2465_CR8","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1093\/brain\/awp144","volume":"132","author":"A Mildner","year":"2009","unstructured":"Mildner A, Mack M, Schmidt H et al (2009) CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain 132:2487\u20132500. https:\/\/doi.org\/10.1093\/brain\/awp144","journal-title":"Brain"},{"key":"2465_CR9","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1097\/WNF.0b013e3181cbf825","volume":"33","author":"J Chun","year":"2010","unstructured":"Chun J, Hartung H-P (2010) Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol 33:91\u2013101. https:\/\/doi.org\/10.1097\/WNF.0b013e3181cbf825","journal-title":"Clin Neuropharmacol"},{"key":"2465_CR10","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1080\/14656566.2018.1434143","volume":"19","author":"M Pitteri","year":"2018","unstructured":"Pitteri M, Magliozzi R, Bajrami A et al (2018) Potential neuroprotective effect of Fingolimod in multiple sclerosis and its association with clinical variables. Expert Opin Pharmacother 19:387\u2013395. https:\/\/doi.org\/10.1080\/14656566.2018.1434143","journal-title":"Expert Opin Pharmacother"},{"key":"2465_CR11","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1111\/jnc.14313","volume":"144","author":"SA O\u2019Sullivan","year":"2018","unstructured":"O\u2019Sullivan SA, O\u2019Sullivan C, Healy LM et al (2018) Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from astrocytes and microglia. J Neurochem 144:736\u2013747. https:\/\/doi.org\/10.1111\/jnc.14313","journal-title":"J Neurochem"},{"key":"2465_CR12","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1007\/s40263-019-00675-7","volume":"33","author":"M Golan","year":"2019","unstructured":"Golan M, Mausner-Fainberg K, Ibrahim B et al (2019) Fingolimod increases brain-derived neurotrophic factor level secretion from circulating T cells of patients with multiple sclerosis. CNS Drugs 33:1229\u20131237. https:\/\/doi.org\/10.1007\/s40263-019-00675-7","journal-title":"CNS Drugs"},{"key":"2465_CR13","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1177\/1352458515574895","volume":"21","author":"F Luessi","year":"2015","unstructured":"Luessi F, Kraus S, Trinschek B et al (2015) FTY720 (fingolimod) treatment tips the balance towards less immunogenic antigen-presenting cells in patients with multiple sclerosis. Mult Scler 21:1811\u20131822. https:\/\/doi.org\/10.1177\/1352458515574895","journal-title":"Mult Scler"},{"key":"2465_CR14","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000157","volume":"2","author":"M Di Dario","year":"2015","unstructured":"Di Dario M, Colombo E, Govi C et al (2015) Myeloid cells as target of fingolimod action in multiple sclerosis. Neurol Neuroimmunol neuroinflammation 2:e157. https:\/\/doi.org\/10.1212\/NXI.0000000000000157","journal-title":"Neurol Neuroimmunol neuroinflammation"},{"key":"2465_CR15","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1161\/CIRCRESAHA.107.170779","volume":"102","author":"JE Hughes","year":"2008","unstructured":"Hughes JE, Srinivasan S, Lynch KR et al (2008) Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages. Circ Res 102:950\u2013958. https:\/\/doi.org\/10.1161\/CIRCRESAHA.107.170779","journal-title":"Circ Res"},{"key":"2465_CR16","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.4049\/jimmunol.0901586","volume":"184","author":"J Michaud","year":"2010","unstructured":"Michaud J, Im D-S, Hla T (2010) Inhibitory role of sphingosine 1-phosphate receptor 2 in macrophage recruitment during inflammation. J Immunol 184:1475\u20131483. https:\/\/doi.org\/10.4049\/jimmunol.0901586","journal-title":"J Immunol"},{"key":"2465_CR17","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/ana.22366","volume":"69","author":"CH Polman","year":"2011","unstructured":"Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292\u2013302. https:\/\/doi.org\/10.1002\/ana.22366","journal-title":"Ann Neurol"},{"key":"2465_CR18","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1212\/WNL.0000000000000283","volume":"82","author":"VG Jokubaitis","year":"2014","unstructured":"Jokubaitis VG, Li V, Kalincik T et al (2014) Fingolimod after natalizumab and the risk of short-term relapse. Neurology 82:1204\u20131211. https:\/\/doi.org\/10.1212\/WNL.0000000000000283","journal-title":"Neurology"},{"key":"2465_CR19","doi-asserted-by":"publisher","first-page":"153ra131","DOI":"10.1126\/scitranslmed.3004186","volume":"4","author":"L Ottoboni","year":"2012","unstructured":"Ottoboni L, Keenan BT, Tamayo P et al (2012) An RNA profile identifies two subsets of multiple sclerosis patients differing in disease activity. Sci Transl Med 4:153ra131. https:\/\/doi.org\/10.1126\/scitranslmed.3004186","journal-title":"Sci Transl Med"},{"key":"2465_CR20","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1001\/jamaneurol.2013.5486","volume":"71","author":"CJ Bevan","year":"2014","unstructured":"Bevan CJ, Cree BAC (2014) Disease activity free status: a new end point for a new era in multiple sclerosis clinical research? JAMA Neurol 71:269\u2013270. https:\/\/doi.org\/10.1001\/jamaneurol.2013.5486","journal-title":"JAMA Neurol"},{"key":"2465_CR21","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1007\/s00415-015-7978-y","volume":"263","author":"L Kappos","year":"2016","unstructured":"Kappos L, Radue E-W, Chin P et al (2016) Onset of clinical and MRI efficacy occurs early after fingolimod treatment initiation in relapsing multiple sclerosis. J Neurol 263:354\u2013360. https:\/\/doi.org\/10.1007\/s00415-015-7978-y","journal-title":"J Neurol"},{"key":"2465_CR22","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nbt.3519","volume":"34","author":"NL Bray","year":"2016","unstructured":"Bray NL, Pimentel H, Melsted P, Pachter L (2016) Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol 34:525\u2013527. https:\/\/doi.org\/10.1038\/nbt.3519","journal-title":"Nat Biotechnol"},{"key":"2465_CR23","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.12688\/f1000research.7563.2","volume":"4","author":"C Soneson","year":"2015","unstructured":"Soneson C, Love MI, Robinson MD (2015) Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences. F1000Res 4:1521. https:\/\/doi.org\/10.12688\/f1000research.7563.2","journal-title":"F1000Res"},{"key":"2465_CR24","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8","journal-title":"Genome Biol"},{"key":"2465_CR25","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/sim.4780090710","volume":"9","author":"Y Hochberg","year":"1990","unstructured":"Hochberg Y, Benjamini Y (1990) More powerful procedures for multiple significance testing. Stat Med 9:811\u2013818. https:\/\/doi.org\/10.1002\/sim.4780090710","journal-title":"Stat Med"},{"key":"2465_CR26","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1007\/s00415-018-8791-1","volume":"265","author":"F Esposito","year":"2018","unstructured":"Esposito F, Ferr\u00e8 L, Clarelli F et al (2018) Effectiveness and baseline factors associated to fingolimod response in a real-world study on multiple sclerosis patients. J Neurol 265:896\u2013905. https:\/\/doi.org\/10.1007\/s00415-018-8791-1","journal-title":"J Neurol"},{"key":"2465_CR27","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx356","author":"J Wang","year":"2017","unstructured":"Wang J, Vasaikar S, Shi Z et al (2017) WebGestalt 2017: a more comprehensive, powerful, flexible and interactive gene set enrichment analysis toolkit. Nucleic Acids Res. https:\/\/doi.org\/10.1093\/nar\/gkx356","journal-title":"Nucleic Acids Res"},{"key":"2465_CR28","doi-asserted-by":"publisher","first-page":"278","DOI":"10.3389\/fphys.2013.00278","volume":"4","author":"C Mitrea","year":"2013","unstructured":"Mitrea C, Taghavi Z, Bokanizad B et al (2013) Methods and approaches in the topology-based analysis of biological pathways. Front Physiol 4:278. https:\/\/doi.org\/10.3389\/fphys.2013.00278","journal-title":"Front Physiol"},{"key":"2465_CR29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005187","volume":"12","author":"L Koumakis","year":"2016","unstructured":"Koumakis L, Kanterakis A, Kartsaki E et al (2016) MinePath: mining for phenotype differential sub-paths in molecular pathways. PLoS Comput Biol 12:e1005187. https:\/\/doi.org\/10.1371\/journal.pcbi.1005187","journal-title":"PLoS Comput Biol"},{"key":"2465_CR30","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1093\/bioinformatics\/btq089","volume":"26","author":"D Beisser","year":"2010","unstructured":"Beisser D, Klau GW, Dandekar T et al (2010) BioNet: an R-Package for the functional analysis of biological networks. Bioinformatics 26:1129\u20131130. https:\/\/doi.org\/10.1093\/bioinformatics\/btq089","journal-title":"Bioinformatics"},{"key":"2465_CR31","doi-asserted-by":"publisher","first-page":"139","DOI":"10.12688\/f1000research.4477.2","volume":"3","author":"G Scardoni","year":"2014","unstructured":"Scardoni G, Tosadori G, Faizan M et al (2014) Biological network analysis with CentiScaPe: centralities and experimental dataset integration. F1000Res 3:139. https:\/\/doi.org\/10.12688\/f1000research.4477.2","journal-title":"F1000Res"},{"key":"2465_CR32","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon P, Markiel A, Ozier O et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498\u20132504. https:\/\/doi.org\/10.1101\/gr.1239303","journal-title":"Genome Res"},{"key":"2465_CR33","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","volume":"37","author":"AM Newman","year":"2019","unstructured":"Newman AM, Steen CB, Liu CL et al (2019) Determining cell type abundance and expression from bulk tissues with digital cytometry. Nat Biotechnol 37:773\u2013782. https:\/\/doi.org\/10.1038\/s41587-019-0114-2","journal-title":"Nat Biotechnol"},{"key":"2465_CR34","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/cns.12793","volume":"24","author":"IC Angerer","year":"2018","unstructured":"Angerer IC, Hecker M, Koczan D et al (2018) Transcriptome profiling of peripheral blood immune cell populations in multiple sclerosis patients before and during treatment with a sphingosine-1-phosphate receptor modulator. CNS Neurosci Ther 24:193\u2013201. https:\/\/doi.org\/10.1111\/cns.12793","journal-title":"CNS Neurosci Ther"},{"key":"2465_CR35","doi-asserted-by":"publisher","first-page":"42087","DOI":"10.1038\/srep42087","volume":"7","author":"J Friess","year":"2017","unstructured":"Friess J, Hecker M, Roch L et al (2017) Fingolimod alters the transcriptome profile of circulating CD4+ cells in multiple sclerosis. Sci Rep 7:42087. https:\/\/doi.org\/10.1038\/srep42087","journal-title":"Sci Rep"},{"key":"2465_CR36","doi-asserted-by":"publisher","first-page":"5511","DOI":"10.1007\/s12035-016-0075-0","volume":"54","author":"L Roch","year":"2017","unstructured":"Roch L, Hecker M, Friess J et al (2017) High-resolution expression profiling of peripheral blood CD8+ cells in patients with multiple sclerosis displays fingolimod-induced immune cell redistribution. Mol Neurobiol 54:5511\u20135525. https:\/\/doi.org\/10.1007\/s12035-016-0075-0","journal-title":"Mol Neurobiol"},{"key":"2465_CR37","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.3389\/fimmu.2018.01693","volume":"9","author":"I Moreno-Torres","year":"2018","unstructured":"Moreno-Torres I, Gonz\u00e1lez-Garc\u00eda C, Marconi M et al (2018) Immunophenotype and transcriptome profile of patients with multiple sclerosis treated with fingolimod: setting up a model for prediction of response in a 2-year translational study. Front Immunol 9:1693. https:\/\/doi.org\/10.3389\/fimmu.2018.01693","journal-title":"Front Immunol"},{"key":"2465_CR38","doi-asserted-by":"publisher","first-page":"e10","DOI":"10.1182\/blood-2009-07-235028","volume":"115","author":"MA Ingersoll","year":"2010","unstructured":"Ingersoll MA, Spanbroek R, Lottaz C et al (2010) Comparison of gene expression profiles between human and mouse monocyte subsets. Blood 115:e10\u2013e19. https:\/\/doi.org\/10.1182\/blood-2009-07-235028","journal-title":"Blood"},{"key":"2465_CR39","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1126\/science.282.5388.480","volume":"282","author":"GJ Randolph","year":"1998","unstructured":"Randolph GJ, Beaulieu S, Lebecque S et al (1998) Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282:480\u2013483. https:\/\/doi.org\/10.1126\/science.282.5388.480","journal-title":"Science"},{"key":"2465_CR40","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.immuni.2013.08.007","volume":"39","author":"C Jakubzick","year":"2013","unstructured":"Jakubzick C, Gautier EL, Gibbings SL et al (2013) Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity 39:599\u2013610. https:\/\/doi.org\/10.1016\/j.immuni.2013.08.007","journal-title":"Immunity"},{"key":"2465_CR41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004204","volume":"4","author":"TS Kim","year":"2009","unstructured":"Kim TS, Braciale TJ (2009) Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses. PLoS ONE 4:e4204. https:\/\/doi.org\/10.1371\/journal.pone.0004204","journal-title":"PLoS ONE"},{"key":"2465_CR42","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.immuni.2012.08.026","volume":"37","author":"E Zigmond","year":"2012","unstructured":"Zigmond E, Varol C, Farache J et al (2012) Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity 37:1076\u20131090. https:\/\/doi.org\/10.1016\/j.immuni.2012.08.026","journal-title":"Immunity"},{"key":"2465_CR43","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.chom.2009.10.007","volume":"6","author":"TM Hohl","year":"2009","unstructured":"Hohl TM, Rivera A, Lipuma L et al (2009) Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection. Cell Host Microbe 6:470\u2013481. https:\/\/doi.org\/10.1016\/j.chom.2009.10.007","journal-title":"Cell Host Microbe"},{"key":"2465_CR44","doi-asserted-by":"publisher","first-page":"5522","DOI":"10.1182\/blood-2009-04-217489","volume":"114","author":"A-M Sponaas","year":"2009","unstructured":"Sponaas A-M, Freitas do Rosario AP, Voisine C, et al (2009) Migrating monocytes recruited to the spleen play an important role in control of blood stage malaria. Blood 114:5522\u20135531. https:\/\/doi.org\/10.1182\/blood-2009-04-217489","journal-title":"Blood"},{"key":"2465_CR45","doi-asserted-by":"publisher","first-page":"5233","DOI":"10.4049\/jimmunol.171.10.5233","volume":"171","author":"T Nagai","year":"2003","unstructured":"Nagai T, Devergne O, Mueller TF et al (2003) Timing of IFN-beta exposure during human dendritic cell maturation and naive Th cell stimulation has contrasting effects on Th1 subset generation: a role for IFN-beta-mediated regulation of IL-12 family cytokines and IL-18 in naive Th cell differentiation. J Immunol 171:5233\u20135243. https:\/\/doi.org\/10.4049\/jimmunol.171.10.5233","journal-title":"J Immunol"},{"key":"2465_CR46","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12974-017-0817-6","volume":"14","author":"K Thomas","year":"2017","unstructured":"Thomas K, Sehr T, Proschmann U et al (2017) Fingolimod additionally acts as immunomodulator focused on the innate immune system beyond its prominent effects on lymphocyte recirculation. J Neuroinflammation 14:41. https:\/\/doi.org\/10.1186\/s12974-017-0817-6","journal-title":"J Neuroinflammation"},{"key":"2465_CR47","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1002\/eji.200425556","volume":"35","author":"H M\u00fcller","year":"2005","unstructured":"M\u00fcller H, Hofer S, Kaneider N et al (2005) The immunomodulator FTY720 interferes with effector functions of human monocyte-derived dendritic cells. Eur J Immunol 35:533\u2013545. https:\/\/doi.org\/10.1002\/eji.200425556","journal-title":"Eur J Immunol"},{"key":"2465_CR48","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.trim.2008.07.004","volume":"20","author":"YY Lan","year":"2008","unstructured":"Lan YY, Tokita D, Wang Z et al (2008) Sphingosine 1-phosphate receptor agonism impairs skin dendritic cell migration and homing to secondary lymphoid tissue: association with prolonged allograft survival. Transpl Immunol 20:88\u201394. https:\/\/doi.org\/10.1016\/j.trim.2008.07.004","journal-title":"Transpl Immunol"},{"key":"2465_CR49","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s00439-010-0789-4","volume":"127","author":"RL Zuvich","year":"2010","unstructured":"Zuvich RL, McCauley JL, Oksenberg JR et al (2010) Genetic variation in the IL7RA\/IL7 pathway increases multiple sclerosis susceptibility. Hum Genet 127:525\u2013535. https:\/\/doi.org\/10.1007\/s00439-010-0789-4","journal-title":"Hum Genet"},{"key":"2465_CR50","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/ng2068","volume":"39","author":"JA Todd","year":"2007","unstructured":"Todd JA, Walker NM, Cooper JD et al (2007) Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 39:857\u2013864. https:\/\/doi.org\/10.1038\/ng2068","journal-title":"Nat Genet"},{"key":"2465_CR51","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1111\/j.1399-0039.2009.01342.x","volume":"74","author":"C O\u2019Doherty","year":"2009","unstructured":"O\u2019Doherty C, Alloza I, Rooney M, Vandenbroeck K (2009) IL7RA polymorphisms and chronic inflammatory arthropathies. Tissue Antigens 74:429\u2013431. https:\/\/doi.org\/10.1111\/j.1399-0039.2009.01342.x","journal-title":"Tissue Antigens"},{"key":"2465_CR52","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/gene.2009.55","volume":"10","author":"M Heron","year":"2009","unstructured":"Heron M, Grutters JC, van Moorsel CHM et al (2009) Variation in IL7R predisposes to sarcoid inflammation. Genes Immun 10:647\u2013653. https:\/\/doi.org\/10.1038\/gene.2009.55","journal-title":"Genes Immun"},{"key":"2465_CR53","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.jdermsci.2009.05.001","volume":"55","author":"S Hoffjan","year":"2009","unstructured":"Hoffjan S, Beygo J, Akkad DA et al (2009) Analysis of variation in the IL7RA and IL2RA genes in atopic dermatitis. J Dermatol Sci 55:138\u2013140. https:\/\/doi.org\/10.1016\/j.jdermsci.2009.05.001","journal-title":"J Dermatol Sci"},{"key":"2465_CR54","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/ng.789","volume":"43","author":"GF Mells","year":"2011","unstructured":"Mells GF, Floyd JAB, Morley KI et al (2011) Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet 43:329\u2013332. https:\/\/doi.org\/10.1038\/ng.789","journal-title":"Nat Genet"},{"key":"2465_CR55","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/nm.2077","volume":"16","author":"X Liu","year":"2010","unstructured":"Liu X, Leung S, Wang C et al (2010) Crucial role of interleukin-7 in T helper type 17 survival and expansion in autoimmune disease. Nat Med 16:191\u2013197. https:\/\/doi.org\/10.1038\/nm.2077","journal-title":"Nat Med"},{"key":"2465_CR56","doi-asserted-by":"publisher","first-page":"3892","DOI":"10.1182\/blood.v99.11.3892","volume":"99","author":"TJ Fry","year":"2002","unstructured":"Fry TJ, Mackall CL (2002) Interleukin-7: from bench to clinic. Blood 99:3892\u20133904. https:\/\/doi.org\/10.1182\/blood.v99.11.3892","journal-title":"Blood"},{"key":"2465_CR57","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.4049\/jimmunol.149.6.2035","volume":"149","author":"TJ Standiford","year":"1992","unstructured":"Standiford TJ, Strieter RM, Allen RM et al (1992) IL-7 up-regulates the expression of IL-8 from resting and stimulated human blood monocytes. J Immunol 149:2035\u20132039","journal-title":"J Immunol"},{"key":"2465_CR58","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1084\/jem.173.4.923","volume":"173","author":"MR Alderson","year":"1991","unstructured":"Alderson MR, Tough TW, Ziegler SF, Grabstein KH (1991) Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes. J Exp Med 173:923\u2013930. https:\/\/doi.org\/10.1084\/jem.173.4.923","journal-title":"J Exp Med"},{"key":"2465_CR59","doi-asserted-by":"publisher","first-page":"5256","DOI":"10.4049\/jimmunol.1201675","volume":"190","author":"Z Chen","year":"2013","unstructured":"Chen Z, Kim S, Chamberlain ND et al (2013) The novel role of IL-7 ligation to IL-7 receptor in myeloid cells of rheumatoid arthritis and collagen-induced arthritis. J Immunol 190:5256\u20135266. https:\/\/doi.org\/10.4049\/jimmunol.1201675","journal-title":"J Immunol"},{"key":"2465_CR60","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1189\/jlb.0506357","volume":"80","author":"MJ Lorenowicz","year":"2006","unstructured":"Lorenowicz MJ, van Gils J, de Boer M et al (2006) Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis. J Leukoc Biol 80:1542\u20131552. https:\/\/doi.org\/10.1189\/jlb.0506357","journal-title":"J Leukoc Biol"},{"issue":"6472","key":"2465_CR61","doi-asserted-by":"publisher","first-page":"eaax9198","DOI":"10.1126\/science.aax9198","volume":"366","author":"M Uhlen","year":"2019","unstructured":"Uhlen M, Karlsson MJ, Zhong W et al (2019) A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science 366(6472):eaax9198. https:\/\/doi.org\/10.1126\/science.aax9198","journal-title":"Science"},{"key":"2465_CR62","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1093\/hmg\/ddt489","volume":"23","author":"G Disanto","year":"2014","unstructured":"Disanto G, Kjetil Sandve G, Ricigliano VAG et al (2014) DNase hypersensitive sites and association with multiple sclerosis. Hum Mol Genet 23:942\u2013948. https:\/\/doi.org\/10.1093\/hmg\/ddt489","journal-title":"Hum Mol Genet"},{"key":"2465_CR63","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12974-015-0460-z","volume":"12","author":"MA Mazzola","year":"2015","unstructured":"Mazzola MA, Raheja R, Murugaiyan G et al (2015) Identification of a novel mechanism of action of fingolimod (FTY720) on human effector T cell function through TCF-1 upregulation. J Neuroinflammation 12:245. https:\/\/doi.org\/10.1186\/s12974-015-0460-z","journal-title":"J Neuroinflammation"},{"key":"2465_CR64","doi-asserted-by":"publisher","first-page":"4575","DOI":"10.1038\/s41467-019-12393-1","volume":"10","author":"H Al-Mossawi","year":"2019","unstructured":"Al-Mossawi H, Yager N, Taylor CA et al (2019) Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele. Nat Commun 10:4575. https:\/\/doi.org\/10.1038\/s41467-019-12393-1","journal-title":"Nat Commun"},{"key":"2465_CR65","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/s0955-0674(99)80031-3","volume":"11","author":"Q Eastman","year":"1999","unstructured":"Eastman Q, Grosschedl R (1999) Regulation of LEF-1\/TCF transcription factors by Wnt and other signals. Curr Opin Cell Biol 11:233\u2013240. https:\/\/doi.org\/10.1016\/s0955-0674(99)80031-3","journal-title":"Curr Opin Cell Biol"},{"key":"2465_CR66","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/nature03319","volume":"434","author":"T Reya","year":"2005","unstructured":"Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434:843\u2013850. https:\/\/doi.org\/10.1038\/nature03319","journal-title":"Nature"},{"key":"2465_CR67","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/s1074-7613(00)00004-2","volume":"13","author":"T Reya","year":"2000","unstructured":"Reya T, O\u2019Riordan M, Okamura R et al (2000) Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity 13:15\u201324. https:\/\/doi.org\/10.1016\/s1074-7613(00)00004-2","journal-title":"Immunity"},{"key":"2465_CR68","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.immuni.2012.08.009","volume":"37","author":"S Yu","year":"2012","unstructured":"Yu S, Zhou X, Steinke FC et al (2012) The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity 37:813\u2013826. https:\/\/doi.org\/10.1016\/j.immuni.2012.08.009","journal-title":"Immunity"},{"key":"2465_CR69","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/j.1749-6632.2011.06302.x","volume":"1247","author":"H-H Xue","year":"2012","unstructured":"Xue H-H, Zhao D-M (2012) Regulation of mature T cell responses by the Wnt signaling pathway. Ann N Y Acad Sci 1247:16\u201333. https:\/\/doi.org\/10.1111\/j.1749-6632.2011.06302.x","journal-title":"Ann N Y Acad Sci"},{"key":"2465_CR70","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1002\/eji.200738118","volume":"38","author":"FJT Staal","year":"2008","unstructured":"Staal FJT, Sen JM (2008) The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur J Immunol 38:1788\u20131794. https:\/\/doi.org\/10.1002\/eji.200738118","journal-title":"Eur J Immunol"},{"key":"2465_CR71","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1189\/jlb.0905539","volume":"79","author":"L Tickenbrock","year":"2006","unstructured":"Tickenbrock L, Schw\u00e4ble J, Strey A et al (2006) Wnt signaling regulates transendothelial migration of monocytes. J Leukoc Biol 79:1306\u20131313. https:\/\/doi.org\/10.1189\/jlb.0905539","journal-title":"J Leukoc Biol"},{"key":"2465_CR72","doi-asserted-by":"publisher","first-page":"7252","DOI":"10.4049\/jimmunol.1000672","volume":"185","author":"L van de Laar","year":"2010","unstructured":"van de Laar L, van den Bosch A, van der Kooij SW et al (2010) A nonredundant role for canonical NF-\u03baB in human myeloid dendritic cell development and function. J Immunol 185:7252\u20137261. https:\/\/doi.org\/10.4049\/jimmunol.1000672","journal-title":"J Immunol"},{"issue":"Pt 1","key":"2465_CR73","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1042\/bj3040087","volume":"304","author":"M Frankenberger","year":"1994","unstructured":"Frankenberger M, Pforte A, Sternsdorf T et al (1994) Constitutive nuclear NF-kappa B in cells of the monocyte lineage. Biochem J 304(Pt 1):87\u201394. https:\/\/doi.org\/10.1042\/bj3040087","journal-title":"Biochem J"},{"key":"2465_CR74","doi-asserted-by":"publisher","first-page":"5573","DOI":"10.1128\/IAI.67.11.5573-5578.1999","volume":"67","author":"S Takashiba","year":"1999","unstructured":"Takashiba S, Van Dyke TE, Amar S et al (1999) Differentiation of monocytes to macrophages primes cells for lipopolysaccharide stimulation via accumulation of cytoplasmic nuclear factor kappaB. Infect Immun 67:5573\u20135578. https:\/\/doi.org\/10.1128\/IAI.67.11.5573-5578.1999","journal-title":"Infect Immun"},{"key":"2465_CR75","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1600-065X.2012.01100.x","volume":"246","author":"EW Harhaj","year":"2012","unstructured":"Harhaj EW, Dixit VM (2012) Regulation of NF-\u03baB by deubiquitinases. Immunol Rev 246:107\u2013124. https:\/\/doi.org\/10.1111\/j.1600-065X.2012.01100.x","journal-title":"Immunol Rev"},{"key":"2465_CR76","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1742-2094-9-15","volume":"9","author":"G Ellrichmann","year":"2012","unstructured":"Ellrichmann G, Th\u00f6ne J, Lee D-H et al (2012) Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation. J Neuroinflammation 9:15. https:\/\/doi.org\/10.1186\/1742-2094-9-15","journal-title":"J Neuroinflammation"},{"key":"2465_CR77","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jim.2016.02.015","volume":"432","author":"A Steimle","year":"2016","unstructured":"Steimle A, Kalbacher H, Maurer A et al (2016) A novel approach for reliable detection of cathepsin S activities in mouse antigen presenting cells. J Immunol Methods 432:87\u201394. https:\/\/doi.org\/10.1016\/j.jim.2016.02.015","journal-title":"J Immunol Methods"},{"key":"2465_CR78","doi-asserted-by":"publisher","first-page":"2421","DOI":"10.1111\/j.1582-4934.2010.01229.x","volume":"15","author":"D Haves-Zburof","year":"2011","unstructured":"Haves-Zburof D, Paperna T, Gour-Lavie A et al (2011) Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis. J Cell Mol Med 15:2421\u20132429. https:\/\/doi.org\/10.1111\/j.1582-4934.2010.01229.x","journal-title":"J Cell Mol Med"},{"key":"2465_CR79","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1097\/FPC.0b013e3281299169","volume":"17","author":"I Grossman","year":"2007","unstructured":"Grossman I, Avidan N, Singer C et al (2007) Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers. Pharmacogenet Genomics 17:657\u2013666. https:\/\/doi.org\/10.1097\/FPC.0b013e3281299169","journal-title":"Pharmacogenet Genomics"},{"key":"2465_CR80","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.clpt.2005.08.018","volume":"78","author":"S Cunningham","year":"2005","unstructured":"Cunningham S, Graham C, Hutchinson M et al (2005) Pharmacogenomics of responsiveness to interferon IFN-beta treatment in multiple sclerosis: a genetic screen of 100 type I interferon-inducible genes. Clin Pharmacol Ther 78:635\u2013646. https:\/\/doi.org\/10.1016\/j.clpt.2005.08.018","journal-title":"Clin Pharmacol Ther"},{"key":"2465_CR81","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/j.autrev.2013.02.006","volume":"12","author":"A Karagkouni","year":"2013","unstructured":"Karagkouni A, Alevizos M, Theoharides TC (2013) Effect of stress on brain inflammation and multiple sclerosis. Autoimmun Rev 12:947\u2013953. https:\/\/doi.org\/10.1016\/j.autrev.2013.02.006","journal-title":"Autoimmun Rev"},{"key":"2465_CR82","doi-asserted-by":"publisher","first-page":"760","DOI":"10.3389\/fimmu.2020.00760","volume":"11","author":"J van Langelaar","year":"2020","unstructured":"van Langelaar J, Rijvers L, Smolders J, van Luijn MM (2020) B and T cells driving multiple sclerosis: identity, mechanisms and potential triggers. Front Immunol 11:760. https:\/\/doi.org\/10.3389\/fimmu.2020.00760","journal-title":"Front Immunol"},{"key":"2465_CR83","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.4049\/jimmunol.179.3.1577","volume":"179","author":"Y Kurashima","year":"2007","unstructured":"Kurashima Y, Kunisawa J, Higuchi M et al (2007) Sphingosine 1-phosphate-mediated trafficking of pathogenic Th2 and mast cells for the control of food allergy. J Immunol 179:1577\u20131585. https:\/\/doi.org\/10.4049\/jimmunol.179.3.1577","journal-title":"J Immunol"},{"key":"2465_CR84","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/all.12082","volume":"68","author":"A Kleinjan","year":"2013","unstructured":"Kleinjan A, van Nimwegen M, Leman K et al (2013) Topical treatment targeting sphingosine-1-phosphate and sphingosine lyase abrogates experimental allergic rhinitis in a murine model. Allergy 68:204\u2013212. https:\/\/doi.org\/10.1111\/all.12082","journal-title":"Allergy"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-021-02465-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-021-02465-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-021-02465-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T18:55:17Z","timestamp":1672599317000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-021-02465-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,28]]},"references-count":84,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["2465"],"URL":"https:\/\/doi.org\/10.1007\/s12035-021-02465-z","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,28]]},"assertion":[{"value":"11 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The local independent Ethical Committee approved the study protocol and all patients signed the informed consent before enrolling in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval and Consent to Participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"G. Sferruzza, F. Clarelli, E. Mascia, L. Ferr\u00e8, L. Ottoboni, M. Sorosina, S. Santoro, P. Provero report no competing financial interest.L. Moiola received honoraria for speaking or partecipating to advisory board from TEVA, Novartis, Biogen, Sanofi e Roche.V. Martinelli has received honoraria for consulting services or speaking activity from Biogen, Merck, Novartis, TEVA, Almirall, and Genzyme.G. Comi has received G. Comi has received personal compensation for consulting and speaking activities from Novartis, Teva, Sanofi Genzyme, Merck, Biogen, Roche, Almirall, Celgene, Forward Pharma, Medday and Excemed.F. Martinelli Boneschi has received compensation for activities with Teva Neuroscience, Biogen Idec, Merck Serono as speaker and\/or advisor.M Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and\/or speaking activities from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).F. Esposito received honoraria from Novartis and received research support from the Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and European Union (Horizon 2020 Research and Innovation programme).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}