| First Author | Kroner A | Year | 2009 |
| Journal | Neurobiol Dis | Volume | 33 |
| Issue | 1 | Pages | 96-103 |
| PubMed ID | 18996482 | Mgi Jnum | J:145018 |
| Mgi Id | MGI:3833177 | Doi | 10.1016/j.nbd.2008.09.021 |
| Citation | Kroner A, et al. (2009) The co-inhibitory molecule PD-1 modulates disease severity in a model for an inherited, demyelinating neuropathy. Neurobiol Dis 33(1):96-103 |
| abstractText | We have previously shown that mice heterozygously deficient for P0 are characterized by a late onset myelin disorder implicating CD8+ T-lymphocytes and macrophages. We now investigated the impact of the co-inhibitory molecule 'programmed death' (PD)-1 (CD279), a CD28-related receptor expressed on activated T- and B-lymphocytes on the pathogenic phenotype of CD8+ T-lymphocytes in the P0 myelin mutants. PD-1 deficiency in P0+/- mice leads to a stronger increase of CD8+ T-lymphocytes and a substantially aggravated histological phenotype in the PNS compared to P0+/- mice expressing PD-1. Correspondingly, functional down-stream features, such as electrophysiological parameters, walking coordination and mechano-sensation are more affected than in PD-1-expressing myelin mutants. Our study demonstrates that a monogenic nerve disorder can be substantially modified by immune-controlling mechanisms. Thus, understanding the implication of disease-modifiers in inherited demyelination could be of pivotal interest for limiting the detrimental impact of primarily genetically-mediated myelin disorders by fostering immuno-regulatory pathways. |
