@article {1360126,
	title = {Inflammatory Stress Causes N-Glycan Processing Deficiency in Ocular Autoimmune Disease},
	journal = {Am J Pathol},
	volume = {189},
	number = {2},
	year = {2019},
	month = {2019 Feb},
	pages = {283-294},
	abstract = {High levels of proinflammatory cytokines have been associated with a loss of tissue function in ocular autoimmune diseases, but the basis for this relationship remains poorly understood. Here we investigate a new role for tumor necrosis factor 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 involved in the biosynthesis of N-glycans. Tumor necrosis factor α but not IL-1β had a profound effect in suppressing the expression of enzymes involved in the Golgi branching pathway, including N-acetylglucosaminyltransferases 1 and 2, which are required for the formation of biantennary structures. This decrease in gene expression was 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 in the conjunctiva. Together, these data indicate that proinflammatory cytokines differentially influence the expression of N-glycan-processing enzymes in the Golgi and set the stage for future studies to explore the pathophysiology of ocular autoimmune diseases.},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2018.10.012},
	author = {Woodward, Ashley M and Lehoux, Sylvain and Mantelli, Flavio and Di Zazzo, Antonio and Brockhausen, Inka and Bonini, Stefano and Arg{\"u}eso, Pablo}
}
