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

研究成果: Article査読

25 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2383-2394
ページ数12
ジャーナルJournal of Experimental Medicine
209
13
DOI
出版ステータスPublished - 2012 12 17
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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