{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T23:12:19Z","timestamp":1769641939763,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013273","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000}}],"reference-count":101,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DE240100650"],"award-info":[{"award-number":["DE240100650"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP230100025"],"award-info":[{"award-number":["DP230100025"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT190100645"],"award-info":[{"award-number":["FT190100645"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP230100485"],"award-info":[{"award-number":["DP230100485"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Multiple sclerosis (MS) is a neurodegenerative disease in which misdirected, persistent activity of the immune system degrades the protective myelin sheaths of nerve axons. Historically, treatment of MS has relied on disease-modifying therapies that involve immunosuppression, such as targeting of the blood-brain barrier (BBB) to restrict lymphocyte movement. New therapeutic ideas in the development pipeline are instead designed to promote populations of myelin producing cells, oligodendrocytes, by exploiting their innate resilience to the stressors of MS or restoring their numbers. Given the significant advancements made in immunological disease understanding due to mathematical and computational modelling, we sought to develop a platform to (1) interrogate our understanding of the neuroimmunological mechanisms driving MS development and (2) examine the impact of different therapeutic strategies. To this end we propose a novel, open-source, agent-based model of lesion development in the CNS. Our model includes crucial populations of T cells, perivascular macrophages, and oligodendrocytes. We examine the sensitivity of the model to key parameters related to disease targets and conclude that lesion stabilisation can be achieved when targeting the integrated stress response of oligodendrocytes. Most significantly, complete prevention of lesion formation is observed when a combination of approved BBB-permeability targeting therapies and integrated-stress response targeting therapies is administered, suggesting the potential to strike a balance between a patient\u2019s immune inflammation and their reparative capacity. Given that there are many open questions surrounding the etiology and treatment of MS, we hope that this malleable platform serves as a tool for experimentalists and modellers to test and generate further hypotheses regarding this disease.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013273","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T18:48:26Z","timestamp":1768934906000},"page":"e1013273","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic targeting of oligodendrocytes in an agent-based model of multiple sclerosis"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4536-5989","authenticated-orcid":true,"given":"Georgia R.","family":"Weatherley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3360-2214","authenticated-orcid":true,"given":"Robyn P.","family":"Araujo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5119-1711","authenticated-orcid":true,"given":"Samantha J.","family":"Dando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrianne L.","family":"Jenner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"14","key":"pcbi.1013273.ref001","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition","volume":"26","author":"C Walton","year":"2020","journal-title":"Mult Scler."},{"key":"pcbi.1013273.ref002","doi-asserted-by":"crossref","unstructured":"Lassmann H. Axonal injury in multiple sclerosis. 2003.","DOI":"10.1136\/jnnp.74.6.695"},{"issue":"12","key":"pcbi.1013273.ref003","doi-asserted-by":"crossref","DOI":"10.1016\/j.amjmed.2020.05.049","article-title":"Treatment of multiple sclerosis: a review","volume":"133","author":"SL Hauser","year":"2020","journal-title":"Am J Med."},{"issue":"1","key":"pcbi.1013273.ref004","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrneurol.2016.187","article-title":"Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis","volume":"13","author":"T Olsson","year":"2017","journal-title":"Nat Rev Neurol."},{"issue":"12","key":"pcbi.1013273.ref005","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/s41577-022-00718-z","article-title":"The immunology of multiple sclerosis","volume":"22","author":"KE Attfield","year":"2022","journal-title":"Nat Rev Immunol."},{"key":"pcbi.1013273.ref006","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev.immunol.23.021704.115707","article-title":"Immunology of multiple sclerosis","volume":"23","author":"M Sospedra","year":"2005","journal-title":"Annu Rev Immunol."},{"issue":"6","key":"pcbi.1013273.ref007","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q","article-title":"Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination","volume":"47","author":"C Lucchinetti","year":"2000","journal-title":"Ann Neurol."},{"issue":"1","key":"pcbi.1013273.ref008","first-page":"1","article-title":"Multiple sclerosis: pathogenesis, symptoms, diagnoses and cell-based therapy","volume":"19","author":"N Ghasemi","year":"2017","journal-title":"Cell J."},{"issue":"4","key":"pcbi.1013273.ref009","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S1474-4422(14)70305-9","article-title":"Role of the innate and adaptive immune responses in the course of multiple sclerosis","volume":"14","author":"B Hemmer","year":"2015","journal-title":"Lancet Neurol."},{"key":"pcbi.1013273.ref010","doi-asserted-by":"crossref","first-page":"760","DOI":"10.3389\/fimmu.2020.00760","article-title":"B and T cells driving multiple sclerosis: identity, mechanisms and potential triggers","volume":"11","author":"J van Langelaar","year":"2020","journal-title":"Front Immunol."},{"issue":"1","key":"pcbi.1013273.ref011","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S1474-4422(23)00377-0","article-title":"Blood-brain barrier dysfunction in multiple sclerosis: causes, consequences, and potential effects of therapies","volume":"23","author":"B Zierfuss","year":"2024","journal-title":"Lancet Neurol."},{"issue":"3","key":"pcbi.1013273.ref012","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/jnc.14270","article-title":"Chemical hypoxia-induced integrated stress response activation in oligodendrocytes is mediated by the transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2)","volume":"144","author":"N Teske","year":"2018","journal-title":"J Neurochem."},{"issue":"1","key":"pcbi.1013273.ref013","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a020479","article-title":"Oligodendrocytes: myelination and axonal support","volume":"8","author":"M Simons","year":"2015","journal-title":"Cold Spring Harb Perspect Biol."},{"issue":"1","key":"pcbi.1013273.ref014","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ncl.2004.09.001","article-title":"Managing symptoms of multiple sclerosis","volume":"23","author":"RT Schapiro","year":"2005","journal-title":"Neurol Clin."},{"issue":"2","key":"pcbi.1013273.ref015","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1177\/1352458517751049","article-title":"ECTRIMS\/EAN Guideline on the pharmacological treatment of people with multiple sclerosis","volume":"24","author":"X Montalban","year":"2018","journal-title":"Mult Scler."},{"issue":"4","key":"pcbi.1013273.ref016","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1212\/WNL.46.4.907","article-title":"Defining the clinical course of multiple sclerosis: results of an international survey","volume":"46","author":"FD Lublin","year":"1996","journal-title":"Neurology."},{"issue":"10","key":"pcbi.1013273.ref017","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S1474-4422(07)70243-0","article-title":"Primary-progressive multiple sclerosis","volume":"6","author":"DH Miller","year":"2007","journal-title":"Lancet Neurol."},{"issue":"9","key":"pcbi.1013273.ref018","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nri3871","article-title":"Immunopathology of multiple sclerosis","volume":"15","author":"CA Dendrou","year":"2015","journal-title":"Nat Rev Immunol."},{"issue":"8","key":"pcbi.1013273.ref019","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/jama.2020.26858","article-title":"Diagnosis and treatment of multiple sclerosis: a review","volume":"325","author":"MP McGinley","year":"2021","journal-title":"JAMA."},{"issue":"9","key":"pcbi.1013273.ref020","first-page":"604","article-title":"Multiple sclerosis: progress, but no cure","volume":"40","author":"K Gohil","year":"2015","journal-title":"P T."},{"issue":"1","key":"pcbi.1013273.ref021","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41582-018-0082-z","article-title":"Treatment of multiple sclerosis - success from bench to bedside","volume":"15","author":"M Tintore","year":"2019","journal-title":"Nat Rev Neurol."},{"issue":"11","key":"pcbi.1013273.ref022","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/s41582-022-00724-8","article-title":"Beyond ocrelizumab in primary progressive multiple sclerosis","volume":"18","author":"T Williams","year":"2022","journal-title":"Nat Rev Neurol."},{"issue":"88","key":"pcbi.1013273.ref023","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.adg7597","article-title":"Integrin \u03b13 promotes TH17 cell polarization and extravasation during autoimmune neuroinflammation","volume":"8","author":"E Park","year":"2023","journal-title":"Sci Immunol."},{"issue":"11","key":"pcbi.1013273.ref024","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1007\/s00415-011-6116-8","article-title":"Progressive multifocal leukoencephalopathy and natalizumab","volume":"258","author":"K Hellwig","year":"2011","journal-title":"J Neurol."},{"issue":"5","key":"pcbi.1013273.ref025","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1007\/s43440-024-00642-0","article-title":"Multiple sclerosis: a narrative overview of current pharmacotherapies and emerging treatment prospects","volume":"76","author":"P Olejnik","year":"2024","journal-title":"Pharmacol Rep."},{"issue":"1","key":"pcbi.1013273.ref026","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41540-020-00165-3","article-title":"Integrative computational approach identifies drug targets in CD4+ T-cell-mediated immune disorders","volume":"7","author":"BL Puniya","year":"2021","journal-title":"NPJ Syst Biol Appl."},{"issue":"4","key":"pcbi.1013273.ref027","first-page":"327","article-title":"Oligodendrocyte development and regenerative therapeutics in multiple sclerosis","volume":"11","author":"N Gacem","year":"2021","journal-title":"Life (Basel)."},{"key":"pcbi.1013273.ref028","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.65469","article-title":"Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment","volume":"10","author":"Y Chen","year":"2021","journal-title":"Elife."},{"key":"pcbi.1013273.ref029","article-title":"Stem cell treatments and multiple sclerosis","volume":"340","author":"RJM Franklin","year":"2010","journal-title":"BMJ."},{"issue":"4","key":"pcbi.1013273.ref030","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1177\/1352458507087324","article-title":"Stem cell therapy in multiple sclerosis: promise and controversy","volume":"14","author":"ID Duncan","year":"2008","journal-title":"Mult Scler."},{"issue":"86","key":"pcbi.1013273.ref031","first-page":"53","article-title":"Strategies for protecting oligodendrocytes and enhancing remyelination in multiple sclerosis","volume":"16","author":"JM Rodgers","year":"2013","journal-title":"Discov Med."},{"key":"pcbi.1013273.ref032","doi-asserted-by":"crossref","first-page":"1389697","DOI":"10.3389\/fneur.2024.1389697","article-title":"Stem cell therapies: a new era in the treatment of multiple sclerosis","volume":"15","author":"L Wu","year":"2024","journal-title":"Front Neurol."},{"issue":"8","key":"pcbi.1013273.ref033","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s11538-023-01181-0","article-title":"Could mathematics be the key to unlocking the mysteries of multiple sclerosis?","volume":"85","author":"G Weatherley","year":"2023","journal-title":"Bull Math Biol."},{"issue":"1","key":"pcbi.1013273.ref034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0000150","article-title":"The origins of concentric demyelination: self-organization in the human brain","volume":"2","author":"RH Khonsari","year":"2007","journal-title":"PLoS One."},{"key":"pcbi.1013273.ref035","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.mcm.2007.06.011","article-title":"Mathematical description of concentric demyelination in the human brain: self-organization models, from Liesegang rings to chemotaxis","volume":"47","author":"V Calvez","year":"2008","journal-title":"Mathematical and Computer Modelling."},{"issue":"2","key":"pcbi.1013273.ref036","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s00285-016-1087-0","article-title":"Demyelination patterns in a mathematical model of multiple sclerosis","volume":"75","author":"MC Lombardo","year":"2017","journal-title":"J Math Biol."},{"key":"pcbi.1013273.ref037","doi-asserted-by":"crossref","first-page":"110532","DOI":"10.1016\/j.jtbi.2020.110532","article-title":"A mathematical model of the multiple sclerosis plaque","volume":"512","author":"N Moise","year":"2021","journal-title":"J Theor Biol."},{"key":"pcbi.1013273.ref038","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/B978-0-444-52001-2.00011-X","article-title":"Multiple sclerosis: diagnosis, differential diagnosis, and clinical presentation","volume":"122","author":"JM Gelfand","year":"2014","journal-title":"Handb Clin Neurol."},{"issue":"3","key":"pcbi.1013273.ref039","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1162\/netn_a_00296","article-title":"Predicting longitudinal brain atrophy in Parkinson\u2019s disease using a susceptible-infected-removed agent-based model","volume":"7","author":"A Abdelgawad","year":"2023","journal-title":"Netw Neurosci."},{"issue":"1","key":"pcbi.1013273.ref040","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12976-020-00123-w","article-title":"An agent-based model to investigate microbial initiation of Alzheimer\u2019s via the olfactory system","volume":"17","author":"S Sundar","year":"2020","journal-title":"Theor Biol Med Model."},{"issue":"3","key":"pcbi.1013273.ref041","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/psp4.13095","article-title":"Microglial roles in Alzheimer\u2019s disease: an agent-based model to elucidate microglial spatiotemporal response to beta-amyloid","volume":"13","author":"C Weathered","year":"2024","journal-title":"CPT Pharmacometrics Syst Pharmacol."},{"key":"pcbi.1013273.ref042","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jim.2015.08.014","article-title":"Agent based modeling of the effects of potential treatments over the blood-brain barrier in multiple sclerosis","volume":"427","author":"M Pennisi","year":"2015","journal-title":"J Immunol Methods."},{"key":"pcbi.1013273.ref043","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-14-S16-S9","article-title":"Agent based modeling of Treg-Teff cross regulation in relapsing-remitting multiple sclerosis","volume":"14","author":"M Pennisi","year":"2013","journal-title":"BMC Bioinformatics."},{"key":"pcbi.1013273.ref044","doi-asserted-by":"crossref","unstructured":"Pennisi M, Russo G, Sgroi G, Palumbo GAP, Pappalardo F. In silico evaluation of daclizumab and vitamin D effects in multiple sclerosis using agent based models. In: International Meeting on Computational Intelligence Methods for Bioinformatics and Biostatistics. 2019. p. 285\u201398.","DOI":"10.1007\/978-3-030-63061-4_25"},{"issue":"3","key":"pcbi.1013273.ref045","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3390\/cells9030586","article-title":"The potential of computational modeling to predict disease course and treatment response in patients with relapsing multiple sclerosis","volume":"9","author":"F Pappalardo","year":"2020","journal-title":"Cells."},{"key":"pcbi.1013273.ref046","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1186\/s12911-022-02034-x","article-title":"In silico clinical trials for relapsing-remitting multiple sclerosis with MS TreatSim","volume":"22","author":"FLP Sips","year":"2022","journal-title":"BMC Med Inform Decis Mak."},{"key":"pcbi.1013273.ref047","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1186\/s12859-020-03776-z","article-title":"Generation of digital patients for the simulation of tuberculosis with UISS-TB","volume":"21","author":"MA Ju\u00e1rez","year":"2020","journal-title":"BMC Bioinformatics."},{"issue":"10","key":"pcbi.1013273.ref048","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0026523","article-title":"SimB16: modeling induced immune system response against B16-melanoma","volume":"6","author":"F Pappalardo","year":"2011","journal-title":"PLoS One."},{"key":"pcbi.1013273.ref049","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1186\/s12859-020-03872-0","article-title":"In silico trial to test COVID-19 candidate vaccines: a case study with UISS platform","volume":"21","author":"G Russo","year":"2020","journal-title":"BMC Bioinformatics."},{"issue":"2","key":"pcbi.1013273.ref050","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jneumeth.2011.08.008","article-title":"A mathematical model of cell death in multiple sclerosis","volume":"201","author":"TM Broome","year":"2011","journal-title":"J Neurosci Methods."},{"issue":"4","key":"pcbi.1013273.ref051","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.copbio.2008.06.011","article-title":"The stochastic nature of biochemical networks","volume":"19","author":"V Shahrezaei","year":"2008","journal-title":"Curr Opin Biotechnol."},{"issue":"2","key":"pcbi.1013273.ref052","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/nrg2509","article-title":"Stochastic modelling for quantitative description of heterogeneous biological systems","volume":"10","author":"DJ Wilkinson","year":"2009","journal-title":"Nat Rev Genet."},{"key":"pcbi.1013273.ref053","unstructured":"Cano RLE, Lopera HDE. Introduction to T and B lymphocytes. Autoimmunity: from bench to bedside. El Rosario University Press; 2013."},{"issue":"1","key":"pcbi.1013273.ref054","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/brain\/awad304","article-title":"Brain perivascular macrophages: current understanding and future prospects","volume":"147","author":"W Wen","year":"2024","journal-title":"Brain."},{"key":"pcbi.1013273.ref055","doi-asserted-by":"crossref","unstructured":"Muller B, Lang S, Dominietto M, Rudin M, Schulz G, Deyhle H, et al. High-resolution tomographic imaging of microvessels. In: Developments in X-ray tomography VI. vol. 7078. SPIE; 2008. p. 89\u201398.","DOI":"10.1117\/12.794157"},{"issue":"2","key":"pcbi.1013273.ref056","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.21037\/qims-21-705","article-title":"Perivascular space is associated with brain atrophy in patients with multiple sclerosis","volume":"12","author":"X-Y Liu","year":"2022","journal-title":"Quant Imaging Med Surg."},{"issue":"7","key":"pcbi.1013273.ref057","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1093\/brain\/awz144","article-title":"Assessment of lesions on magnetic resonance imaging in multiple sclerosis: practical guidelines","volume":"142","author":"M Filippi","year":"2019","journal-title":"Brain."},{"issue":"4","key":"pcbi.1013273.ref058","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1159\/000382130","article-title":"Multiple sclerosis relapses: epidemiology, outcomes and management. a systematic review","volume":"44","author":"T Kalincik","year":"2015","journal-title":"Neuroepidemiology."},{"issue":"1","key":"pcbi.1013273.ref059","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1002\/ana.1032","article-title":"Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis","volume":"50","author":"WI McDonald","year":"2001","journal-title":"Ann Neurol."},{"issue":"5","key":"pcbi.1013273.ref060","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/ana.25463","article-title":"Silent progression in disease activity-free relapsing multiple sclerosis","volume":"85","author":"BAC Cree","year":"2019","journal-title":"Ann Neurol."},{"key":"pcbi.1013273.ref061","article-title":"The natural history of relapses in multiple sclerosis","author":"T Vollmer","year":"2007","journal-title":"J Neurol Sci."},{"key":"pcbi.1013273.ref062","doi-asserted-by":"crossref","first-page":"676686","DOI":"10.3389\/fimmu.2021.676686","article-title":"Memory B cells in multiple sclerosis: emerging players in disease pathogenesis","volume":"12","author":"KD DiSano","year":"2021","journal-title":"Front Immunol."},{"key":"pcbi.1013273.ref063","doi-asserted-by":"crossref","first-page":"760","DOI":"10.3389\/fimmu.2020.00760","article-title":"B and T cells driving multiple sclerosis: identity, mechanisms and potential triggers","volume":"11","author":"J van Langelaar","year":"2020","journal-title":"Front Immunol."},{"key":"pcbi.1013273.ref064","doi-asserted-by":"crossref","first-page":"676686","DOI":"10.3389\/fimmu.2021.676686","article-title":"Memory B cells in multiple sclerosis: emerging players in disease pathogenesis","volume":"12","author":"KD DiSano","year":"2021","journal-title":"Front Immunol."},{"issue":"3","key":"pcbi.1013273.ref065","doi-asserted-by":"crossref","first-page":"27","DOI":"10.5493\/wjem.v4.i3.27","article-title":"Multiple sclerosis and the role of immune cells","volume":"4","author":"RA H\u00f8glund","year":"2014","journal-title":"World J Exp Med."},{"key":"pcbi.1013273.ref066","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1752-0509-5-114","article-title":"Modeling the effector - regulatory T cell cross-regulation reveals the intrinsic character of relapses in multiple sclerosis","volume":"5","author":"N V\u00e9lez de Mendiz\u00e1bal","year":"2011","journal-title":"BMC Syst Biol."},{"issue":"7","key":"pcbi.1013273.ref067","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1093\/brain\/awy151","article-title":"The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells","volume":"141","author":"J Machado-Santos","year":"2018","journal-title":"Brain."},{"issue":"10","key":"pcbi.1013273.ref068","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1177\/0271678X221101643","article-title":"Heterogeneity and developmental dynamics of LYVE-1 perivascular macrophages distribution in the mouse brain","volume":"42","author":"M Karam","year":"2022","journal-title":"J Cereb Blood Flow Metab."},{"issue":"7","key":"pcbi.1013273.ref069","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1007\/s11538-010-9585-5","article-title":"A theory of immunodominance and adaptive regulation","volume":"73","author":"PS Kim","year":"2011","journal-title":"Bull Math Biol."},{"key":"pcbi.1013273.ref070","doi-asserted-by":"crossref","DOI":"10.30707\/LiB5.2Jennera","article-title":"Modelling combined virotherapy and immunotherapy: strengthening the antitumour immune response mediated by IL-12 and GM-CSF expression","volume":"5","author":"AL Jenner","year":"2018","journal-title":"Letters in Biomathematics."},{"issue":"3","key":"pcbi.1013273.ref071","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/imm.13320","article-title":"Monocytes, macrophages, dendritic cells and neutrophils: an update on lifespan kinetics in health and disease","volume":"163","author":"AA Patel","year":"2021","journal-title":"Immunology."},{"issue":"2","key":"pcbi.1013273.ref072","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1006\/exnr.2000.7618","article-title":"Turnover of rat brain perivascular cells","volume":"168","author":"I Bechmann","year":"2001","journal-title":"Exp Neurol."},{"issue":"3","key":"pcbi.1013273.ref073","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nri.2015.16","article-title":"T cell migration, search strategies and mechanisms","volume":"16","author":"MF Krummel","year":"2016","journal-title":"Nat Rev Immunol."},{"issue":"6","key":"pcbi.1013273.ref074","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1002\/(SICI)1521-4141(199906)29:06<2037::AID-IMMU2037>3.0.CO;2-V","article-title":"Switch in chemokine receptor expression upon TCR stimulation reveals novel homing potential for recently activated T cells","volume":"29","author":"F Sallusto","year":"1999","journal-title":"Eur J Immunol."},{"issue":"1","key":"pcbi.1013273.ref075","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/sj.cr.7290265","article-title":"Signaling mechanisms for regulation of chemotaxis","volume":"15","author":"D Wu","year":"2005","journal-title":"Cell Res."},{"issue":"12","key":"pcbi.1013273.ref076","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1111\/cns.13954","article-title":"Perivascular macrophages in the CNS: from health to neurovascular diseases","volume":"28","author":"L Zheng","year":"2022","journal-title":"CNS Neurosci Ther."},{"issue":"1","key":"pcbi.1013273.ref077","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/cns.13569","article-title":"Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms","volume":"27","author":"X Huang","year":"2021","journal-title":"CNS Neurosci Ther."},{"issue":"8","key":"pcbi.1013273.ref078","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.arcmed.2014.11.013","article-title":"Role of the blood\u2013brain barrier in multiple sclerosis","volume":"45","author":"GG Ortiz","year":"2014","journal-title":"Archives of Medical Research."},{"issue":"5","key":"pcbi.1013273.ref079","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.humimm.2020.02.009","article-title":"The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis","volume":"81","author":"R Balasa","year":"2020","journal-title":"Hum Immunol."},{"issue":"2","key":"pcbi.1013273.ref080","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.bbadis.2010.09.010","article-title":"Cells of the oligodendroglial lineage, myelination, and remyelination","volume":"1812","author":"VE Miron","year":"2011","journal-title":"Biochim Biophys Acta."},{"key":"pcbi.1013273.ref081","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.neuropharm.2015.10.010","article-title":"Oligodendrocyte regeneration: its significance in myelin replacement and neuroprotection in multiple sclerosis","volume":"110","author":"KA Chamberlain","year":"2016","journal-title":"Neuropharmacology."},{"issue":"5","key":"pcbi.1013273.ref082","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.2353\/ajpath.2008.080449","article-title":"Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma","volume":"173","author":"W Lin","year":"2008","journal-title":"Am J Pathol."},{"issue":"4","key":"pcbi.1013273.ref083","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/S1474-4422(15)00381-6","article-title":"Harnessing the integrated stress response for the treatment of multiple sclerosis","volume":"15","author":"SW Way","year":"2016","journal-title":"Lancet Neurol."},{"issue":"6","key":"pcbi.1013273.ref084","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1038\/s41380-022-01512-y","article-title":"Chronic stress disrupts the homeostasis and progeny progression of oligodendroglial lineage cells, associating immune oligodendrocytes with prefrontal cortex hypomyelination","volume":"27","author":"AG Kokkosis","year":"2022","journal-title":"Mol Psychiatry."},{"issue":"2","key":"pcbi.1013273.ref085","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.celrep.2017.09.050","article-title":"Remarkable stability of myelinating oligodendrocytes in mice","volume":"21","author":"RB Tripathi","year":"2017","journal-title":"Cell Rep."},{"key":"pcbi.1013273.ref086","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2016.01.005","article-title":"Adult oligodendrocyte progenitor cells - multifaceted regulators of the CNS in health and disease","volume":"57","author":"A Fernandez-Castaneda","year":"2016","journal-title":"Brain Behav Immun."},{"key":"pcbi.1013273.ref087","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ceb.2021.05.003","article-title":"Oligodendrocyte progenitor cell fate and function in development and disease","volume":"73","author":"BLL Clayton","year":"2021","journal-title":"Curr Opin Cell Biol."},{"issue":"12","key":"pcbi.1013273.ref088","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.4103\/1673-5374.262569","article-title":"Turning to myelin turnover","volume":"14","author":"TJ Buscham","year":"2019","journal-title":"Neural Regen Res."},{"issue":"1","key":"pcbi.1013273.ref089","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12974-016-0635-2","article-title":"New insights into the pharmacokinetics and pharmacodynamics of natalizumab treatment for patients with multiple sclerosis, obtained from clinical and in vitro studies","volume":"13","author":"T Sehr","year":"2016","journal-title":"J Neuroinflammation."},{"issue":"6","key":"pcbi.1013273.ref090","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1137\/140955823","article-title":"Modeling and analysis of recurrent autoimmune disease","volume":"74","author":"W Zhang","year":"2014","journal-title":"SIAM J Appl Math."},{"key":"pcbi.1013273.ref091","doi-asserted-by":"crossref","first-page":"105529","DOI":"10.1016\/j.cnsns.2020.105529","article-title":"Revealing the role of the effector-regulatory t cell loop on autoimmune disease symptoms via nonlinear analysis","volume":"93","author":"W Zhang","year":"2021","journal-title":"Communications in Nonlinear Science and Numerical Simulation."},{"issue":"6","key":"pcbi.1013273.ref092","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s00285-023-02017-0","article-title":"The effect of chemotaxis on T-cell regulatory dynamics","volume":"87","author":"MC Dallaston","year":"2023","journal-title":"J Math Biol."},{"issue":"6231","key":"pcbi.1013273.ref093","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1126\/science.aaa4484","article-title":"Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit","volume":"348","author":"I Das","year":"2015","journal-title":"Science."},{"issue":"2","key":"pcbi.1013273.ref094","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1093\/brain\/awy322","article-title":"Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis","volume":"142","author":"Y Chen","year":"2019","journal-title":"Brain."},{"key":"pcbi.1013273.ref095","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.65469","article-title":"Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment","volume":"10","author":"Y Chen","year":"2021","journal-title":"Elife."},{"issue":"39","key":"pcbi.1013273.ref096","doi-asserted-by":"crossref","first-page":"12151","DOI":"10.1073\/pnas.1506654112","article-title":"Signal strength regulates antigen-mediated T-cell deceleration by distinct mechanisms to promote local exploration or arrest","volume":"112","author":"HD Moreau","year":"2015","journal-title":"Proc Natl Acad Sci U S A."},{"key":"pcbi.1013273.ref097","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.48051","article-title":"Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry","volume":"8","author":"V Ramaglia","year":"2019","journal-title":"Elife."},{"issue":"4","key":"pcbi.1013273.ref098","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1007\/s11481-014-9544-2","article-title":"PET imaging in multiple sclerosis","volume":"9","author":"P Faria D de","year":"2014","journal-title":"J Neuroimmune Pharmacol."},{"issue":"11","key":"pcbi.1013273.ref099","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/s41582-021-00537-1","article-title":"Positron emission tomography in multiple sclerosis - straight to the target","volume":"17","author":"B Bodini","year":"2021","journal-title":"Nat Rev Neurol."},{"issue":"3","key":"pcbi.1013273.ref100","article-title":"Quantification of spatial and phenotypic heterogeneity in an agent-based model of tumour-macrophage interactions","volume":"19","author":"JA Bull","year":"2023","journal-title":"PLoS Comput Biol."},{"issue":"1","key":"pcbi.1013273.ref101","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41540-024-00419-4","article-title":"Spatial computational modelling illuminates the role of the tumour microenvironment for treating glioblastoma with immunotherapies","volume":"10","author":"B Mongeon","year":"2024","journal-title":"NPJ Syst Biol Appl."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1013273","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013273","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T18:56:25Z","timestamp":1769540185000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013273"}},"subtitle":[],"editor":[{"given":"Sophia","family":"Rudorf","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":101,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1013273","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,20]]}}}