title: Dysregulated upregulation of T-cell immunoglobulin and mucin domain-3 on mucosal T helper 1 cells in patients with Crohn's disease.
abstract: OBJECTIVE
  T-cell immunoglobulin and mucin domain-3 (TIM-3) is a unique cell surface molecule expressed on T helper 1 (Th1) cells. Engagement of TIM-3 by ligand galectin-9 leads to dampened Th1 immunity. We investigated TIM-3 and galectin-9 expression in inflammatory bowel disease (IBD) patients and in healthy controls, and evaluated the immune role of the TIM-3 pathway in Crohn's disease (CD) pathogenesis.
  
  
  METHODS
  We used flow cytometry to investigate TIM-3 expression on mononuclear cells isolated from the intestinal mucosa and peripheral blood cells of patients with IBD and healthy controls. We also evaluated galectin-9 mRNA expression on endoscopically obtained intestinal mucosal cells.
  
  
  RESULTS
  TIM-3 was constitutively expressed on Th cells isolated from the intestinal mucosa of IBD patients and healthy controls. While we observed low TIM-3 expression on Th cells isolated from peripheral blood mononuclear cells (PBMCs), high TIM-3 expression was induced by Th1 stimulation. The level of TIM-3 expression on Th cells isolated from intestinal mucosa and stimulated PBMCs was significantly lower in CD patients than in healthy controls.
  
  
  CONCLUSIONS
  Our data show that TIM-3 upregulation on Th1 cells is dysregulated in patients with CD. Low TIM-3 expression on Th1 cells may provide a clue toward resolution of the inflammation associated with chronic inflammatory disease. These findings should contribute to develop understanding of CD pathogenesis.
authors.affiliation: Department of Gastroenterology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Morimoto
authors.forename: Shuhei
authors.initials: S
authors.lastname: Hosomi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Yamagami
authors.forename: Kenji
authors.initials: K
authors.lastname: Watanabe
authors.forename: Noriko
authors.initials: N
authors.lastname: Kamata
authors.forename: Mitsue
authors.initials: M
authors.lastname: Sogawa
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Machida
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Okazaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nagahara
authors.forename: Eiji
authors.initials: E
authors.lastname: Noda
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tominaga
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Maeda
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D001706:Biopsy; D003424:Crohn Disease / Q000276:immunology*; D005434:Flow Cytometry; D037161:Galectins / Q000235:genetics; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger