title: Glucosamine induces activated T cell apoptosis through reduced T cell receptor.
abstract: Glucosamine (GlcN), like N-acetylglucosamine (GlcNAc), is salvaged into the hexosamine pathway and is converted to UDP-GlcNAc. Golgi N-glycan branching enzymes produce N-glycans, using UDP-GlcNAc as a substrate, which attach to the T cell receptor (TCR) and cytotoxic T-lymphocyte antigen-4 (CTLA-4). These findings suggest that GlcN exerts the immunoregulation through TCR signalling, which could be involved not only in cytokine production but also activated T cell apoptosis. In fact, a preliminary study showed that GlcN reduced the number of CD3+ T cells of NC/Nga mice with AD-like skin lesions. Therefore, whether apoptosis of T cells would be one of the potential molecular mechanisms of GlcN-induced immunosuppression was investigated. Cultured human primary along with Jurkat T cells and purified T cells from NC/Nga mice with or without Df-induced AD-like skin lesion were used for the study. Glucosamine treatment increased the number of T cells expressing β1,6GlcNAc-branched N-glycans, with reduced ZAP-70 phosphorylation and enhanced CTLA-4 expression. Glucosamine treatment reduced the number of activated T cells from both the human primary and Jurkat cells and the dermatitis-induced mice. The expression of FasL and activated caspases, particularly caspase-3, was increased, whereas the phosphorylation of PI3K, Akt and NF-κB was decreased by GlcN treatment. Therefore, in addition to down-regulating TCR signalling and promoting CTLA-4 expression, GlcN may also suppress T cell function by enhancing apoptosis of activated T cells, through both extrinsic and intrinsic apoptotic signalling pathways, which were regulated by the inhibition of PI3K/Akt and NF-κB phosphorylation.
authors.affiliation: Department of Dermatology, School of Medicine, Dongguk University Ilsan Hospital, Gyeonggi-do, South Korea.
authors.forename: N-H
authors.initials: NH
authors.lastname: Chen
authors.forename: K A
authors.initials: KA
authors.lastname: Cheong
authors.forename: C-H
authors.initials: CH
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Noh
authors.forename: A-Y
authors.initials: AY
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D060908:CTLA-4 Antigen / Q000032:analysis; D005944:Glucosamine / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D019869:Phosphatidylinositol 3-Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; D005944:Glucosamine