{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:05:08Z","timestamp":1791968708786,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T00:00:00Z","timestamp":1666915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)","award":["CRC SFB 1009 A03"],"award-info":[{"award-number":["CRC SFB 1009 A03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pericytes at the blood\u2013brain barrier (BBB) are located between the tight endothelial cell layer of the blood vessels and astrocytic endfeet. They contribute to central nervous system (CNS) homeostasis by regulating BBB development and maintenance. Loss of pericytes results in increased numbers of infiltrating immune cells in the CNS in experimental autoimmune encephalomyelitis (EAE), the mouse model for multiple sclerosis (MS). However, little is known about their competence to modulate immune cell activation or function in CNS autoimmunity. To evaluate the capacity of pericytes to directly interact with T cells in an antigen-specific fashion and potentially (re)shape their function, we depleted major histocompatibility complex (MHC) class II from pericytes in a cell type-specific fashion and performed T cell-pericyte cocultures and EAE experiments. We found that pericytes present antigen in vitro to induce T cell activation and proliferation. In an adoptive transfer EAE experiment, pericyte-specific MHC II KO resulted in locally enhanced T cell infiltration in the CNS; even though, overall disease course of mice was not affected. Thus, pericytes may serve as non-professional antigen-presenting cells affecting states of T cell activation, thereby locally shaping lesion formation in CNS inflammation but without modulating disease severity.<\/jats:p>","DOI":"10.3390\/ijms232113081","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T04:57:34Z","timestamp":1667105854000},"page":"13081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["CNS Pericytes Modulate Local T Cell Infiltration in EAE"],"prefix":"10.3390","volume":"23","author":[{"given":"Kathrin","family":"Koch","sequence":"first","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Lindner","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Katrin","family":"Fleck","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5565-5325","authenticated-orcid":false,"given":"Marie","family":"Liebmann","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4287-2678","authenticated-orcid":false,"given":"Melanie","family":"Eschborn","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6760-4499","authenticated-orcid":false,"given":"Lisa","family":"Zondler","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Di\u00e9guez-Hurtado","sequence":"additional","affiliation":[{"name":"Department of Tissue Morphogenesis, Faculty of Medicine, Max Planck Institute for Molecular Biomedicine, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf H.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Tissue Morphogenesis, Faculty of Medicine, Max Planck Institute for Molecular Biomedicine, University of Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4341-4719","authenticated-orcid":false,"given":"Gerd","family":"Meyer zu H\u00f6rste","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Zarbock","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Kuhlmann","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Wiendl","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Klotz","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University Hospital Muenster, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature09522","article-title":"Pericytes Regulate the Blood\u2013Brain Barrier","volume":"468","author":"Armulik","year":"2010","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature13165","article-title":"Capillary Pericytes Regulate Cerebral Blood Flow in Health and Disease","volume":"508","author":"Hall","year":"2014","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.neuron.2010.09.043","article-title":"Pericytes Control Key Neurovascular Functions and Neuronal Phenotype in the Adult Brain and during Brain Aging","volume":"68","author":"Bell","year":"2010","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nature09513","article-title":"Pericytes Are Required for Blood\u2013Brain Barrier Integrity during Embryogenesis","volume":"468","author":"Daneman","year":"2010","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nrn.2017.48","article-title":"v Cerebral Blood Flow Regulation and Neurovascular Dysfunction in Alzheimer Disease","volume":"18","author":"Kisler","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/jcbfm.2015.44","article-title":"Accelerated Pericyte Degeneration and Blood-Brain Barrier Breakdown in Apolipoprotein E4 Carriers with Alzheimer\u2019s Disease","volume":"36","author":"Halliday","year":"2016","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1177\/0271678X17690761","article-title":"Differing Associations between A\u03b2 Accumulation, Hypoperfusion, Blood-Brain Barrier Dysfunction and Loss of PDGFRB Pericyte Marker in the Precuneus and Parietal White Matter in Alzheimer\u2019s Disease","volume":"38","author":"Miners","year":"2018","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1001\/jamaneurol.2014.4636","article-title":"Vascular Plasticity and Cognition During Normal Aging and Dementia","volume":"72","author":"Montagne","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5196","DOI":"10.1038\/s41467-020-19042-y","article-title":"Transplantation of HPSC-Derived Pericyte-like Cells Promotes Functional Recovery in Ischemic Stroke Mice","volume":"11","author":"Sun","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1038\/nm.2022","article-title":"Pericyte Contraction Induced by Oxidative-Nitrative Stress Impairs Capillary Reflow despite Successful Opening of an Occluded Cerebral Artery","volume":"15","author":"Yemisci","year":"2009","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/ana.24512","article-title":"Pericytes Are Involved in the Pathogenesis of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy","volume":"78","author":"Ghosh","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ayres-Sander, C.E., Lauridsen, H., Maier, C.L., Sava, P., Pober, J.S., and Gonzalez, A.L. (2013). Transendothelial Migration Enables Subsequent Transmigration of Neutrophils through Underlying Pericytes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060025"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1084\/jem.20111622","article-title":"Pericytes Support Neutrophil Subendothelial Cell Crawling and Breaching of Venular Walls in Vivo","volume":"209","author":"Proebstl","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/ni.2477","article-title":"Capillary and Arteriolar Pericytes Attract Innate Leukocytes Exiting through Venules and \u201cinstruct\u201d Them with Pattern-Recognition and Motility Programs","volume":"14","author":"Stark","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, S., Cao, C., Chen, Z., Bankaitis, V., Tzima, E., Sheibani, N., and Burridge, K. (2012). Pericytes Regulate Vascular Basement Membrane Remodeling and Govern Neutrophil Extravasation during Inflammation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045499"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2016587118","DOI":"10.1073\/pnas.2016587118","article-title":"Pericytes Regulate Vascular Immune Homeostasis in the CNS","volume":"118","author":"Schreiner","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","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":"Hemmer","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/nature08478","article-title":"Effector T Cell Interactions with Meningeal Vascular Structures in Nascent Autoimmune CNS Lesions","volume":"462","author":"Kawakami","year":"2009","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.4049\/jimmunol.181.7.4648","article-title":"Swift Entry of Myelin-Specific T Lymphocytes into the Central Nervous System in Spontaneous Autoimmune Encephalomyelitis","volume":"181","author":"Furtado","year":"2008","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/nm1197","article-title":"Dendritic Cells Permit Immune Invasion of the CNS in an Animal Model of Multiple Sclerosis","volume":"11","author":"Greter","year":"2005","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nri.2016.144","article-title":"T Cell Responses in the Central Nervous System","volume":"17","author":"Korn","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1002\/sctm.17-0028","article-title":"Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination","volume":"6","author":"Iacobaeus","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.celrep.2017.08.007","article-title":"Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination","volume":"20","author":"Lange","year":"2017","journal-title":"Cell Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1038\/s41467-019-10643-w","article-title":"Loss of the Transcription Factor RBPJ Induces Disease-Promoting Properties in Brain Pericytes","volume":"10","author":"Kato","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.it.2012.07.004","article-title":"Capture, Crawl, Cross: The T Cell Code to Breach the Blood-Brain Barriers","volume":"33","author":"Engelhardt","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e20191339","DOI":"10.1084\/jem.20191339","article-title":"The Endothelial Basement Membrane Acts as a Checkpoint for Entry of Pathogenic T Cells into the Brain","volume":"217","author":"Zhang","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s12974-021-02358-x","article-title":"Pericytes as Mediators of Infiltration of Macrophages in Multiple Sclerosis","volume":"18","author":"Kaushik","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/hep.21965","article-title":"Tolerogenic Maturation of Liver Sinusoidal Endothelial Cells Promotes B7-Homolog 1-Dependent CD8+ T Cell Tolerance","volume":"47","author":"Diehl","year":"2007","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1002\/hep.24508","article-title":"Cross-Presentation of Antigen by Diverse Subsets of Murine Liver Cells","volume":"54","author":"Ebrahimkhani","year":"2011","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4049\/jimmunol.1600602","article-title":"Human Lung Fibroblasts Present Bacterial Antigens to Autologous Lung Th Cells","volume":"198","author":"Hutton","year":"2017","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1093\/brain\/aws058","article-title":"Licensing of Myeloid Cells Promotes Central Nervous System Autoimmunity and Is Controlled by Peroxisome Proliferator-Activated Receptor \u03b3","volume":"135","author":"Hucke","year":"2012","journal-title":"Brain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"971","DOI":"10.4049\/jimmunol.1300280","article-title":"Tumor-Derived Vascular Pericytes Anergize Th Cells","volume":"191","author":"Bose","year":"2013","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.molmed.2010.11.006","article-title":"EAE: Imperfect but Useful Models of Multiple Sclerosis","volume":"17","author":"Hart","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41583-021-00525-w","article-title":"Emerging Roles for CNS Fibroblasts in Health, Injury and Disease","volume":"23","author":"Dorrier","year":"2022","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nature25739","article-title":"A Molecular Atlas of Cell Types and Zonation in the Brain Vasculature","volume":"554","author":"Vanlandewijck","year":"2018","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1038\/s41467-017-01738-3","article-title":"Pericytes Regulate VEGF-Induced Endothelial Sprouting through VEGFR1","volume":"8","author":"Eilken","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/dvg.20335","article-title":"A Global Double-Fluorescent Cre Reporter Mouse","volume":"45","author":"Muzumdar","year":"2007","journal-title":"Genesis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.mvr.2012.03.008","article-title":"A Novel and Simple Method for Culturing Pericytes from Mouse Brain","volume":"84","author":"Tigges","year":"2012","journal-title":"Microvasc. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E6182","DOI":"10.1073\/pnas.1601350113","article-title":"B7-H1 Shapes t-Cell-Mediated Brain Endothelial Cell Dysfunction and Regional Encephalitogenicity in Spontaneous CNS Autoimmunity","volume":"113","author":"Klotz","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An Open-Source Platform for Biological-Image Analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_41","first-page":"e52924","article-title":"Quantitation of Endothelial Cell Adhesiveness In Vitro","volume":"2015","author":"Lowe","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1084\/jem.20021603","article-title":"Myelin Oligodendrocyte Glycoprotein\u2013Specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis","volume":"197","author":"Bettelli","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1046\/j.1440-1711.1998.00709.x","article-title":"Defective TCR Expression in Transgenic Mice Constructed Using CDNA-Based \u03b1- and \u03b2-Chain Genes under the Control of Heterologous Regulatory Elements","volume":"76","author":"Barnden","year":"1998","journal-title":"Immunol. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1093\/brain\/awab040","article-title":"Dietary Conjugated Linoleic Acid Links Reduced Intestinal Inflammation to Amelioration of CNS Autoimmunity","volume":"144","author":"Fleck","year":"2021","journal-title":"Brain"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E8017","DOI":"10.1073\/pnas.1721049115","article-title":"Nur77 Serves as a Molecular Brake of the Metabolic Switch during T Cell Activation to Restrict Autoimmunity","volume":"115","author":"Liebmann","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/13081\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:04:42Z","timestamp":1760144682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/13081"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,28]]},"references-count":45,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232113081"],"URL":"https:\/\/doi.org\/10.3390\/ijms232113081","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,28]]}}}