Journal
NEUROBIOLOGY OF DISEASE
Volume 33, Issue 1, Pages 96-103Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2008.09.021
Keywords
Schwann cell; Charcot-Marie-Tooth disease; Myelin; T-lymphocytes; Adaptive immune system; Macrophages
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Funding
- SFB [581]
- University of Wuerzburg
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We have previously shown that mice heterozygously deficient for PO 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 PO 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. (c) 2008 Elsevier Inc. All rights reserved.
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