title: Nogo receptor is involved in the adhesion of dendritic cells to myelin.
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 down-regulated 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.
authors: Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors: Claire L
authors: CL
authors: McDonald
authors: Karin
authors: K
authors: Steinbach
authors: Florian
authors: F
authors: Kern
authors: Rüdiger
authors: R
authors: Schweigreiter
authors: Roland
authors: R
authors: Martin
authors: Christine E
authors: CE
authors: Bandtlow
authors: Markus
authors: M
authors: Reindl
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016131:Lymphocyte Subsets; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D000070817:Nogo Receptor 2; D000070156:Nogo Receptors; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D000070817:Nogo Receptor 2; D000070156:Nogo Receptors; D020033:Protein Isoforms; C000603199:RTN4 protein, human; C474328:RTN4RL1 protein, human; C474327:RTN4RL2 protein, human; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse; C419790:Rtn4r protein, mouse