Mucopolysaccharidosis IIIB, a lysosomal storage disease, triggers a pathogenic CNS autoimmune response.
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, TNFalpha, IFNalpha 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.
Killedar
Smruti
S
Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.
Dirosario
Julianne
J
Divers
Erin
E
Popovich
Phillip G
PG
McCarty
Douglas M
DM
Fu
Haiyan
H
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D017690:Cell Transplantation; D002490:Central Nervous System / Q000033:anatomy & histology / Q000276:immunology* / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009084:Mucopolysaccharidosis III / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D045442:Rotarod Performance Test; D013154:Spleen / Q000166:cytology
D016207:Cytokines