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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2010

Open Access 01-12-2010 | Research

Mucopolysaccharidosis IIIB, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response

Authors: Smruti Killedar, Julianne DiRosario, Erin Divers, Phillip G Popovich, Douglas M McCarty, Haiyan Fu

Published in: Journal of Neuroinflammation | Issue 1/2010

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Abstract

Background

Recently, using a mouse model of mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease with severe neurological deterioration, we showed that MPS IIIB neuropathology is accompanied by a robust neuroinflammatory response of unknown consequence. This study was to assess whether MPS IIIB lymphocytes are pathogenic.

Methods

Lymphocytes from MPS IIIB mice were adoptively transferred to naïve wild-type mice. The recipient animals were then evaluated for signs of disease and inflammation in the central nervous system.

Results

Our results show for the first time, that lymphocytes isolated from MPS IIIB mice caused a mild paralytic disease when they were injected systemically into naïve wild-type mice. This disease is characterized by mild tail and lower trunk weakness with delayed weight gain. The MPS IIIB lymphocytes also trigger neuroinflammation within the CNS of recipient mice characterized by an increase in transcripts of IL2, IL4, IL5, IL17, TNFα, IFNα and Ifi30, and intraparenchymal lymphocyte infiltration.

Conclusions

Our data suggest that an autoimmune response directed at CNS components contributes to MPS IIIB neuropathology independent of lysosomal storage pathology. Adoptive transfer of purified T-cells will be needed in future studies to identify specific effector T-cells in MPS IIIB neuroimmune pathogenesis.
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Metadata
Title
Mucopolysaccharidosis IIIB, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response
Authors
Smruti Killedar
Julianne DiRosario
Erin Divers
Phillip G Popovich
Douglas M McCarty
Haiyan Fu
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2010
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-7-39

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