title: Role of Sortilin in Models of Autoimmune Neuroinflammation.
abstract: The proneurotrophin receptor sortilin is a protein with dual functions, being involved in intracellular protein transport, as well as cellular signal transduction. The relevance of the receptor for various neuronal disorders, such as dementia, seizures, and brain injury, is well established. In contrast, little is known about the role of sortilin in immune cells and inflammatory diseases. The aim of our study was to elucidate the distribution of sortilin in different immune cell types in mice and humans and to analyze its function in autoimmune CNS inflammation. Sortilin was expressed most profoundly in murine and human macrophages and dendritic cells and to a much lesser extent in B and T cells. In dendritic cells, sortilin had an impact on Ag processing. Accordingly, sortilin was highly expressed by infiltrated perivascular myeloid cells, mainly in vessel cuffs, in the CNS of patients suffering from multiple sclerosis, the most common inflammatory autoimmune disease of the CNS. Yet, sortilin gene-targeted mice (Sort1(-/-)) and chimeras deficient in sortilin in the immune system were as susceptible as wild-type littermates to T cell-dependent experimental autoimmune encephalomyelitis. Considering our results and recent data from other investigators, we conclude that the proneurotrophin receptor sortilin plays a role in innate, rather than in adaptive, immune processes and, thus, not in autoimmune neuroinflammation.
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
authors.forename: Eva
authors.initials: E
authors.lastname: Reuter
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
authors.forename: Juliane
authors.initials: J
authors.lastname: Weber
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
authors.forename: Magdalena
authors.initials: M
authors.lastname: Paterka
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
authors.forename: Robert
authors.initials: R
authors.lastname: Ploen
authors.affiliation: Molecular Cardiovascular Research, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany; and.
authors.forename: Tilman
authors.identifier: http://orcid.org/0000-0002-1676-7498
authors.initials: T
authors.lastname: Breiderhoff
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center Amsterdam, 1081 BT Amsterdam, the Netherlands.
authors.forename: Jack
authors.initials: J
authors.lastname: van Horssen
authors.affiliation: Molecular Cardiovascular Research, Max Delbrueck Center for Molecular Medicine Berlin-Buch, 13125 Berlin, Germany; and.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Willnow
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany;
authors.forename: Volker
authors.initials: V
authors.lastname: Siffrin
authors.affiliation: Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany; frauke.zipp@unimedizin-mainz.de.
authors.forename: Frauke
authors.identifier: http://orcid.org/0000-0002-1231-1928
authors.initials: F
authors.lastname: Zipp
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics; D001930:Brain Injuries / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology*; D020078:Neurogenic Inflammation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000099183:Sortilin