Innate and adaptive immune activation in the brain of MPS IIIB mouse model
Article first published online: 24 OCT 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 87, Issue 4, pages 978–990, March 2009
How to Cite
DiRosario, J., Divers, E., Wang, C., Etter, J., Charrier, A., Jukkola, P., Auer, H., Best, V., Newsom, D. L., McCarty, D. M. and Fu, H. (2009), Innate and adaptive immune activation in the brain of MPS IIIB mouse model. J. Neurosci. Res., 87: 978–990. doi: 10.1002/jnr.21912
- Issue published online: 12 FEB 2009
- Article first published online: 24 OCT 2008
- Manuscript Accepted: 25 AUG 2008
- Manuscript Revised: 11 AUG 2008
- Manuscript Received: 7 MAY 2008
- TRI-NCH startup fund
- lysosomal storage disease;
- central nervous system (CNS)
Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with severe neurological manifestations due to α-N-acetylglucosaminidase (NaGlu) deficiency. The mechanism of neuropathology in MPS IIIB is unclear. This study investigates the role of immune responses in neurological disease of MPS IIIB in mice. By means of gene expression microarrays and real-time quantitative reverse transcriptase–polymerase chain reaction, we demonstrated significant up-regulation of numerous immune-related genes in MPS IIIB mouse brain involving a broad range of immune cells and molecules, including T cells, B cells, microglia/macrophages, complement, major histocompatibility complex class I, immunoglobulin, Toll-like receptors, and molecules essential for antigen presentation. The significantly enlarged spleen and lymph nodes in MPS IIIB mice were due to an increase in splenocytes/lymphocytes, and functional assays indicated that the T cells were activated. An autoimmune component to the disease was further suggested by the presence of putative autoantigen or autoantigens in brain extracts that reacted specifically with serum IgG from MPS IIIB mice. We also demonstrated for the first time that immunosuppression with prednisolone alone can significantly slow the central nervous system disease progression. Our data indicate that immune responses contribute greatly to the neuropathology of MPS IIIB and should be considered as an adjunct treatment in future therapeutic developments for optimal therapeutic effect. © 2008 Wiley-Liss, Inc.