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

Autor: Phillip G. Popovich, Haiyan Fu, Julianne DiRosario, Erin Divers, Douglas M. McCarty, Smruti Killedar
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Central Nervous System
Adoptive cell transfer
Pathology
medicine.medical_specialty
congenital
hereditary
and neonatal diseases and abnormalities
Cell Transplantation
Mucopolysaccharidosis
Molecular Sequence Data
Immunology
Autoimmunity
Neuropathology
Biology
medicine.disease_cause
lcsh:RC346-429
Pathogenesis
03 medical and health sciences
Mice
Mucopolysaccharidosis III
Cellular and Molecular Neuroscience
0302 clinical medicine
Lysosomal storage disease
medicine
Animals
Humans
Lymphocytes
skin and connective tissue diseases
Neuroinflammation
lcsh:Neurology. Diseases of the nervous system
Mice
Knockout
General Neuroscience
Research
nutritional and metabolic diseases
medicine.disease
Adoptive Transfer
3. Good health
Neurology
Rotarod Performance Test
Cytokines
030217 neurology & neurosurgery
Spleen
030215 immunology
Zdroj: Journal of Neuroinflammation, Vol 7, Iss 1, p 39 (2010)
Journal of Neuroinflammation
ISSN: 1742-2094
Popis: BackgroundRecently, 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.MethodsLymphocytes 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.ResultsOur 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.ConclusionsOur 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.
Databáze: OpenAIRE
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