Nogo receptor is involved in the adhesion of dendritic cells to myelin
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RESEARCH
JOURNAL OF NEUROINFLAMMATION
Open Access
Nogo receptor is involved in the adhesion of dendritic cells to myelin Claire L McDonald1, Karin Steinbach2, Florian Kern3, Rüdiger Schweigreiter3, Roland Martin4, Christine E Bandtlow3 and Markus Reindl1*
Abstract Background: Nogo-66 receptor NgR1 and its structural homologue NgR2 are binding proteins for a number of myelin-associated inhibitory factors. After neuronal injury, these inhibitory factors are responsible for preventing axonal outgrowth via their interactions with NgR1 and NgR2 expressed on neurons. In vitro, cells expressing NgR1/ 2 are inhibited from adhering to and spreading on a myelin substrate. Neuronal injury also results in the presence of dendritic cells (DCs) in the central nervous system, where they can come into contact with myelin debris. The exact mechanisms of interaction of immune cells with CNS myelin are, however, poorly understood. Methods: Human DCs were differentiated from peripheral blood monocytes and mouse DCs were differentiated from wild type and NgR1/NgR2 double knockout bone marrow precursors. NgR1 and NgR2 expression were determined with quantitative real time PCR and immunoblot, and adhesion of cells to myelin was quantified. Results: We demonstrate that human immature myeloid DCs express NgR1 and NgR2, which are then downregulated upon maturation. Human mature DCs also adhere to a much higher extent to a myelin substrate than immature DCs. We observe the same effect when the cells are plated on Nogo-66-His (binding peptide for NgR1), but not on control proteins. Mature DCs taken from Ngr1/2 knockout mice adhere to a much higher extent to myelin compared to wild type mouse DCs. In addition, Ngr1/2 knockout had no effect on in vitro DC differentiation or phenotype. Conclusions: These results indicate that a lack of NgR1/2 expression promotes the adhesion of DCs to myelin. This interaction could be important in neuroinflammatory disorders such as multiple sclerosis in which peripheral immune cells come into contact with myelin debris. Keywords: Nogo receptor, NgR1, NgR2, Nogo-66, myelin associated glycoprotein, MAG, myelin, dendritic cells
Background Injury to the central nervous system (CNS) has long been known to cause fatal and irreversible damage to axons and neurons. A number of physical and molecular inhibitory factors expressed by neurons, astrocytes, and oligodendrocytes serve to maintain the architecture of the mature CNS, but at the same time contribute to the lack of repair mechanisms following damage. Some of the major molecular inhibitors to regeneration are those associated with myelin (myelin-associated inhibitory factors, MAIFs). MAIFs include Nogo-A [1,2], myelin-associated * Correspondence: [email protected] 1 Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria Full list of author information is available at the end of the article
glycoprotein (MAG) [3,4] and oligodendrocyte-myelin glycoprotein (OMgp) [5]. These factors are all binding part
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