title: Characterisation of the T cell and dendritic cell repertoire in a murine model of mucopolysaccharidosis I (MPS I).
abstract: BACKGROUND
  Mucopolysaccharidosis I (MPS I) is a metabolic disorder caused by α-L-Iduronidase (IDUA) deficiency, resulting in lysosomal accumulation of heparan (HS) and dermatan sulphate (DS). This has been reported in microglia, yet currently the effect of IDUA deficiency on T cells and dendritic cells (DC) and their functionality in disease pathogenesis remains unclear.
  
  
  METHODS
  Peripheral blood was collected from 3 month old C57BL/6 MPS I (n = 11) and wildtype (WT) (n = 6) mice. T cell and DC phenotype and functional characteristics were identified by flow cytometry.
  
  
  RESULTS
  MPS I mice exhibited a reduction in DC (p = <0.001) along with CD8+ cytotoxic (p = 0.01) and CD4+ T helper (p = 0.032) cells, compared to WT controls. MPS I DC displayed a significant decrease in cell surface CD123 (p = 0.02) and CD86 (p = 0.006) expression. Furthermore, CD45RB expression was significantly reduced on T helper cells in the MPS I population (p = 0.019).
  
  
  CONCLUSIONS
  We report a reduction in circulating DC and T cells in the MPS I mouse; indicative of adaptive immune dysfunction. DC reduction may occur in response to down-regulation of the IL-3 receptor (CD123), necessary for DC survival. We also report down-regulation of cell surface CD86, a molecule required for T cell co-stimulation. T helper cell down-regulation of CD45RB is redolent of an anti-inflammatory phenotype with poor proliferative capacity. The definitive causes of our findings and the consequences and role that these findings play in the pathogenesis of MPS are unclear, but may be in response to lysosomal storage of unmetabolized HS and DS.
authors: The Transplant Centre, UHSM, Manchester, UK.
authors: Louise D
authors: LD
authors: Archer
authors: Kia J
authors: KJ
authors: Langford-Smith
authors: William R
authors: WR
authors: Critchley
authors: Brian W
authors: BW
authors: Bigger
authors: James E
authors: JE
authors: Fildes
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008059:Mucopolysaccharidosis I / Q000276:immunology*; D016185:Receptors, Interleukin-3 / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016185:Receptors, Interleukin-3; D017493:Leukocyte Common Antigens