Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells

Atsushi Nishida, Kiyotaka Nagahama, Hirotsugu Imaeda, Atsuhiro Ogawa, Cindy W. Lau, Taku Kobayashi, Tadakazu Hisamatsu, Frederic I. Preffer, Emiko Mizoguchi, Hiroki Ikeuchi, Toshifumi Hibi, Minoru Fukuda, Akira Andoh, Richard S. Blumberg, Atsushi Mizoguchi

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19 Citations (Scopus)

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 exacerba- tion 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.

Original languageEnglish
Pages (from-to)2383-2394
Number of pages12
JournalJournal of Experimental Medicine
Volume209
Issue number13
DOIs
Publication statusPublished - 2012 Dec 17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Nishida, A., Nagahama, K., Imaeda, H., Ogawa, A., Lau, C. W., Kobayashi, T., Hisamatsu, T., Preffer, F. I., Mizoguchi, E., Ikeuchi, H., Hibi, T., Fukuda, M., Andoh, A., Blumberg, R. S., & Mizoguchi, A. (2012). Inducible colitis-associated glycome capable of stimulating the proliferation of memory CD4+ T cells. Journal of Experimental Medicine, 209(13), 2383-2394. https://doi.org/10.1084/jem.20112631