title: Interleukin-2, Interleukin-7, T cell-mediated autoimmunity, and N-glycosylation.
abstract: T cell activation and self-tolerance are tightly regulated to provide effective host defense against foreign pathogens while deflecting inappropriate autoimmune responses. Golgi Asn (N)-linked protein glycosylation coregulates homeostatic set points for T cell growth, differentiation, and self-tolerance to influence risk of autoimmune disorders such as multiple sclerosis (MS). Human autoimmunity is a complex trait that develops from intricate and poorly understood interactions between an individual's genetics and their environmental exposures. Recent evidence from our group suggests that in MS, additive and/or epistatic interactions between multiple genetic and environmental risk factors combine to dysregulate a common biochemical pathway, namely Golgi N-glycosylation. Here, we review the multiple regulatory mechanisms controlling N-glycan branching in T cells and autoimmunity, focusing on recent data implicating a critical role for interleukin-2 (IL-2) and IL-7 signaling.
authors.affiliation: Department of Neurology, University of California, Irvine, USA.
authors.forename: Ani
authors.initials: A
authors.lastname: Grigorian
authors.forename: Haik
authors.initials: H
authors.lastname: Mkhikian
authors.forename: Michael
authors.initials: M
authors.lastname: Demetriou
mesh_terms: D015551:Autoimmunity; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry / Q000276:immunology*; D015851:Interleukin-7 / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics / Q000276:immunology; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D017634:Self Tolerance; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C508594:IL2 protein, human; C508605:IL7 protein, human; D007376:Interleukin-2; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D020395:Receptors, Interleukin-7; C561128:MGAT1 protein, human; D017351:N-Acetylglucosaminyltransferases