title: Glucosamine Modulates T Cell Differentiation through Down-regulating N-Linked Glycosylation of CD25.
abstract: Glucosamine has immunomodulatory effects on autoimmune diseases. However, the mechanism(s) through which glucosamine modulates different T cell subsets and diseases remain unclear. We demonstrate that glucosamine impedes Th1, Th2, and iTreg but promotes Th17 differentiation through down-regulating N-linked glycosylation of CD25 and subsequently inhibiting its downstream Stat5 signaling in a dose-dependent manner. The effect of glucosamine on T helper cell differentiation was similar to that induced by anti-IL-2 treatment, further supporting an IL-2 signaling-dependent modulation. Interestingly, excess glucose rescued this glucosamine-mediated regulation, suggesting a functional competition between glucose and glucosamine. High-dose glucosamine significantly decreased Glut1 N-glycosylation in Th1-polarized cells. This finding suggests that both down-regulated IL-2 signaling and Glut1-dependent glycolytic metabolism contribute to the inhibition of Th1 differentiation by glucosamine. Finally, glucosamine treatment inhibited Th1 cells in vivo, prolonged the survival of islet grafts in diabetic recipients, and exacerbated the severity of EAE. Taken together, our results indicate that glucosamine interferes with N-glycosylation of CD25, and thereby attenuates IL-2 downstream signaling. These effects suggest that glucosamine may be an important modulator of T cell differentiation and immune homeostasis.
authors.affiliation: From the Graduate Institute of Life Sciences, Department and Graduate Institute of Microbiology and Immunology.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Chien
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Department of Biology and Anatomy and Surgery.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology.
authors.forename: Shin-Huei
authors.initials: SH
authors.lastname: Fu
authors.affiliation: From the Graduate Institute of Life Sciences, Department and Graduate Institute of Microbiology and Immunology.
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, 35053 Taiwan.
authors.forename: B Lin-Ju
authors.initials: BL
authors.lastname: Yen
authors.affiliation: Department of Ophthalmology, Tri-Service General Hospital.
authors.forename: Jiann-Torng
authors.initials: JT
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, 11490 Taiwan and.
authors.forename: Deh-Ming
authors.initials: DM
authors.lastname: Chang
authors.affiliation: From the Graduate Institute of Life Sciences, Department and Graduate Institute of Microbiology and Immunology, sytwu@ndmctsgh.edu.tw.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D015536:Down-Regulation; D005260:Female; D005944:Glucosamine / Q000737:chemistry*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006031:Glycosylation; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology; D058504:Th17 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology
chemical_list: D051272:Glucose Transporter Type 1; D053645:Interleukin-2 Receptor alpha Subunit; C495678:Slc2a1 protein, mouse; D005944:Glucosamine
keywords: CD25; Glucosamine; N-linked glycosylation; T helper cells; autoimmune disease; cytokine; diabetes; multiple sclerosis