Journal of Inherited Metabolic Disease

, Volume 36, Issue 2, pp 257–262 | Cite as

Characterisation of the T cell and dendritic cell repertoire in a murine model of mucopolysaccharidosis I (MPS I)

  • Louise D Archer
  • Kia J Langford-Smith
  • William R Critchley
  • Brian W Bigger
  • James E Fildes
Original Article



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.


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.


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).


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.


Dendritic Cell Heparan Sulphate Helper Cell Dermatan Sulphate Cell Repertoire 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Conflict of interest



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Copyright information

© SSIEM and Springer 2012

Authors and Affiliations

  • Louise D Archer
    • 1
  • Kia J Langford-Smith
    • 2
  • William R Critchley
    • 1
  • Brian W Bigger
    • 2
  • James E Fildes
    • 1
    • 3
    • 4
  1. 1.The Transplant CentreUHSMManchesterUK
  2. 2.Stem Cell & Neurotherapies LaboratoryManchesterUK
  3. 3.School of Translational MedicineUniversity of ManchesterManchesterUK
  4. 4.The Transplant CentreUniversity Hospital of South Manchester NHS Foundation TrustManchesterUK

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