Abstract No.: | A-C1098 |
Country: | Canada |
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Title: | NOGO AND NOGO RECEPTOR REGULATION AND SIGNALLING IN HUMAN IMMUNE CELLS |
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Authors/Affiliations: | 1 Madeline Pool*; 1 Isabel Rambaldi; 1 Amit Bar-Or; 1 Alyson E. Fournier;
1 Montreal Neurological Institute, QC, Canada
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Content: | Background: A hallmark of multiple sclerosis (MS) is the infiltration of activated immune cells into sites of demyelination and axonal injury. Axonal repair in the central nervous system (CNS) is hampered by several myelin-associated inhibitory molecules, including MAG, OMgp and Nogo. In the experimental autoimmune encephalomyelitis animal model of MS, neutralization of Nogo or Nogo receptor (NgR1) lessens disease (Fontoura et al. 2004; Karnezis et al. 2004). Surprisingly, in addition to improved axonal recovery, inflammatory infiltrates were also reduced, suggesting that Nogo/NgR1 signals may regulate immune cell responses.
Objective: To determine the role of Nogo and NgR1 in immune cell function.
Materials and Methods: Western blotting and RT-PCR were used to assess the expression of Nogo and NgR1 in immune cells. Adhesion and migration assays were performed to test the ability of immune cells to respond to myelin substrates, a source of NgR1 agonists.
Results: We demonstrate that human immune cell subsets express Nogo and NgR1 in a regulated fashion upon activation. NgR1 expression by immune cells suggests that they may respond to Nogo present in CNS myelin. Indeed, encountering myelin substrates alters immune cell adhesion and migration.
Conclusions: We propose that myelin signals may alter the adhesion properties of immune cells and thereby influence their ability to migrate through the CNS. Nogo and NgR1 would therefore be potential therapeutic targets for both regenerative and immuno-modulatory strategies to repair and prevent the CNS damage in MS.
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