title: Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells.
abstract: Immune responses are modified by a diverse and abundant repertoire of carbohydrate structures on the cell surface, which is known as the glycome. In this study, we propose that a unique glycome that can be identified through the binding of galectin-4 is created on local, but not systemic, memory CD4+ T cells under diverse intestinal inflammatory conditions, but not in the healthy state. The colitis-associated glycome (CAG) represents an immature core 1-expressing O-glycan. Development of CAG may be mediated by down-regulation of the expression of core-2 β1,6-N-acetylglucosaminyltransferase (C2GnT) 1, a key enzyme responsible for the production of core-2 O-glycan branch through addition of N-acetylglucosamine (GlcNAc) to a core-1 O-glycan structure. Mechanistically, the CAG seems to contribute to super raft formation associated with the immunological synapse on colonic memory CD4+ T cells and to the consequent stabilization of protein kinase C θ activation, resulting in the stimulation of memory CD4+ T cell expansion in the inflamed intestine. Functionally, CAG-mediated CD4+ T cell expansion contributes to the exacerbation of T cell-mediated experimental intestinal inflammations. Therefore, the CAG may be an attractive therapeutic target to specifically suppress the expansion of effector memory CD4+ T cells in intestinal inflammation such as that seen in inflammatory bowel disease.
authors.affiliation: Molecular Pathology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nagahama
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Imaeda
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Ogawa
authors.forename: Cindy W
authors.initials: CW
authors.lastname: Lau
authors.forename: Taku
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Hisamatsu
authors.forename: Frederic I
authors.initials: FI
authors.lastname: Preffer
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizoguchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ikeuchi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizoguchi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D004789:Enzyme Activation; D037541:Galectin 4 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D054992:Immunological Synapses / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D011134:Polysaccharides / Q000276:immunology* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D000074121:Protein Kinase C-theta
chemical_list: D037541:Galectin 4; D007527:Isoenzymes; D011134:Polysaccharides; D017351:N-Acetylglucosaminyltransferases; C053024:beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D017493:Leukocyte Common Antigens