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: Eva Reuter, Juliane Weber, Magdalena Paterka, Robert Ploen, Tilman Breiderhoff, Jack van Horssen, Thomas E Willnow, Volker Siffrin, Frauke Zipp
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 195 Issue 12 Pg. 5762-9 (Dec 15 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 26566674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• Adaptor Proteins, Vesicular Transport
• sortilin

Topics

• Adaptor Proteins, Vesicular Transport (genetics, metabolism)
• Animals
• Antigen Presentation (genetics)
• Autoimmunity (genetics)
• Brain Injuries (immunology)
• Central Nervous System (immunology)
• Dendritic Cells (immunology)
• Encephalomyelitis, Autoimmune, Experimental (immunology)
• Humans
• Immunity, Innate
• Macrophages (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Multiple Sclerosis (immunology)
• Neurogenic Inflammation
• Signal Transduction
• T-Lymphocytes (immunology)