Immune system irregularities in lysosomal storage disorders |
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Authors: | Julian A Castaneda Ming J Lim Jonathan D Cooper David A Pearce |
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Institution: | (1) Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 645, Rochester, NY 14642, USA;(2) Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA;(3) Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA;(4) Pediatric Storage Disorders Laboratory, Department of Neuroscience and Centre for the Cellular Basis of Behaviour, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King’s College London, James Black Centre, 125 Coldharbour Lane, SE5 9NU London, UK |
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Abstract: | Lysosomal storage disorders (LSDs) are genetically inherited diseases characterized by the accumulation of disease-specific
biological materials such as proteolipids or metabolic intermediates within the lysosome. The lysosomal compartment’s central
importance to normal cellular function can be appreciated by examining the various pathologies that arise in LSDs. These disorders
are invariably fatal, and many display profound neurological impairment that begins in childhood. However, recent studies
have revealed that several LSDs also have irregularities in the function of the immune system. Gaucher disease, mucopolysaccharidosis
VII, and α-mannosidosis are examples of a subset of LSD patients that are predisposed towards immune suppression. In contrast,
GM2 gangliosidosis, globoid cell leukodystrophy, Niemann-Pick disease type C1 and juvenile neuronal ceroid lipofuscinosis
are LSDs that are predisposed towards immune system hyperactivity. Antigen presentation and processing by dedicated antigen
presenting cells (APCs), secretion of pore-forming perforins by cytotoxic-T lymphocytes, and release of pro-inflammatory mediators
by mast cells are among the many crucial immune system functions in which the lysosome plays a central role. Although the
relationship between the modification of the lysosomal compartment in LSDs and modulation of the immune system remains unknown,
there is emerging evidence for early neuroimmune responses in a variety of LSDs. In this review we bridge biochemical studies
on the lysosomal compartment’s role in the immune system with clinical data on immune system irregularities in a subset of
LSDs. |
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