Pathogenesis of multiple sclerosis via environmental and genetic dysregulation of N-glycosylation.

Autoimmune diseases such as multiple sclerosis (MS) result from complex and
poorly understood interactions of genetic and environmental factors. A central
role for T cells in MS is supported by mouse models, association of the major
histocompatibility complex region, and association of critical T cell growth
regulator genes such as interleukin-2 receptor (IL-2RA) and interleukin-7
receptor (IL-7RA). Multiple environmental factors (vitamin D(3) deficiency and
metabolism) converge with multiple genetic variants (IL-7RA, IL-2RA, MGAT1, and
CTLA-4) to dysregulate Golgi N-glycosylation in MS, resulting in T cell
hyperactivity, loss of self-tolerance and in mice, a spontaneous MS-like disease 
with neurodegeneration. Here, we review the genetic and biological interactions
that regulate MS pathogenesis through dysregulation of N-glycosylation and how
this may enable individualized therapeutic approaches.