title: Immune system irregularities in lysosomal storage disorders.
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 alpha-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.
authors.affiliation: Center for Aging and Developmental Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Julian A
authors.initials: JA
authors.lastname: Castaneda
authors.forename: Ming J
authors.initials: MJ
authors.lastname: Lim
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cooper
authors.forename: David A
authors.initials: DA
authors.lastname: Pearce
mesh_terms: D000818:Animals; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000276:immunology* / Q000473:pathology