Inflammatory stress causes N-glycan processing deficiency in ocular autoimmune disease.

Inflammatory stress causes N-glycan processing deficiency in ocular autoimmune disease. Am J Pathol. 2018 Nov 15;: Authors: Woodward AM, Lehoux S, Mantelli F, Di Zazzo A, Brockhausen I, Bonini S, Argüeso P Abstract High levels of proinflammatory cytokines have been associated with loss of tissue function in ocular autoimmune diseases but the basis for this relationship remains poorly understood. Here we investigated a new role for tumor necrosis factor (TNF)-α in promoting N-glycan processing deficiency at the surface of the eye through inhibition of N-acetylglucosaminyltransferase expression in the Golgi. Using mass spectrometry, complex-type biantennary oligosaccharides were identified as major N-glycan structures in differentiated human corneal epithelial cells. Remarkably, significant differences were detected between the efficacies of cytokines in regulating the expression of glycogenes responsible for the biosynthesis of N-glycans. TNFα but not interleukin-1β had a profound effect in suppressing the expression of enzymes involved in the Golgi branching pathway, including MGAT1 and 2, which are required for the formation of biantennary structures. This decrease in gene expression correlated with a reduction in enzymatic activity and impaired N-glycan branching. Moreover, patients with ocular mucous membrane pemphigoid were characterized by marginal N-acetylglucosaminyltransferase expression and decreased N-glycan branching i...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research