The Role of Innate Immunity in Mucopolysaccharidoses.

Mucopolysaccharidoses are lysosomal storage disorders characterised by accumulation of abnormal pathological glycosaminoglycans, cellular dysfunction and widespread inflammation, resulting in progressive cognitive and motor decline. Lysosomes are important mediators of immune cell function, and therefore accumulation of GAGs and other abnormal substrates could affect immune function and directly impact on disease pathogenesis. This review summarises current knowledge with regards to inflammation in mucopolysaccharidosis with an emphasis on the brain and outlines a potential role for GAGs in induction of inflammation. We propose a model by which the accumulation of GAGs and other factors may impact on innate immune signalling with particular focus on the TLR4 pathway. Innate immunity appears to have a dominating role in MPS; however furthering understanding of innate immune signalling would have significant impact on highlighting novel anti-inflammatory therapeutics for use in MPS disease. This article is protected by copyright. All rights reserved.