AI Article Synopsis
- A lack of the Golgi N-glycan branching enzyme Mgat5 in mice leads to heightened T cell activity, increased endocytosis of CTLA-4, and autoimmune responses similar to multiple sclerosis (MS).
- Genetic and environmental factors linked to MS can lower N-glycan branching in T cells; these include variations in IL2RA and IL7RA genes, as well as vitamin D3 deficiency.
- Intronic variants in MGAT5 are significantly associated with diminished N-glycan branching and CTLA-4 surface expression, contributing to MS risk alongside other genetic factors (p=5.79×10(-9)).
Article Abstract
Deficiency of the Golgi N-glycan branching enzyme Mgat5 in mice promotes T cell hyperactivity, endocytosis of CTLA-4 and autoimmunity, including a spontaneous multiple sclerosis (MS)-like disease. Multiple genetic and environmental MS risk factors lower N-glycan branching in T cells. These include variants in interleukin-2 receptor-α (IL2RA), interleukin-7 receptor-α (IL7RA), and MGAT1, a Golgi branching enzyme upstream of MGAT5, as well as vitamin D3 deficiency and Golgi substrate metabolism. Here we describe linked intronic variants of MGAT5 that are associated with reduced N-glycan branching, CTLA-4 surface expression and MS (p=5.79×10(-9), n=7,741), the latter additive with the MGAT1, IL2RA and IL7RA MS risk variants (p=1.76×10(-9), OR=0.67-1.83, n=3,518).
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528623 | PMC |
| http://dx.doi.org/10.1016/j.jneuroim.2012.12.008 | DOI Listing |
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