title: Expression of human TIM-3 and its correlation with disease activity in rheumatoid arthritis.
abstract: OBJECTIVE
  T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 (Th1)-cell-mediated immunity. This study was undertaken to investigate the expressions of TIM-3 and its ligand galectin 9 (Gal-9) with respect to disease activity in rheumatoid arthritis (RA).
  
  
  METHODS
  Blood was collected from 39 RA patients and 31 healthy controls. Blood leucocyte TIM-3 and Gal-9 mRNA levels and RA disease activity were determined. Synovial tissue (ST) from five RA patients and five osteoarthritis (OA) patients were examined for TIM-3 mRNA expression and were also analysed for TIM-3 by immunohistology.
  
  
  RESULTS
  TIM-3 mRNA expression was significantly higher in the ST of RA patients than in the ST of OA patients. TIM-3 was expressed in the synovial sublining area in ST of RA patients but not in OA ST. TIM-3 mRNA expression from peripheral blood mononuclear cells (PBMCs) of RA patients was negatively correlated with the 28-joint Disease Activity Score (DAS28). Gal-9 mRNA level in PBMCs of RA patients was higher than in healthy controls, and was significantly higher in patients with low disease activity compared to those with moderate to high disease activity. Gal-9 mRNA expression in PBMCs of RA patients was positively correlated with forkhead box P3 (FoxP3) mRNA expression.
  
  
  CONCLUSIONS
  TIM-3 and its interaction with Gal-9 are closely associated with RA disease activity and may play an important role in the pathogenesis of RA. In addition to the negative regulatory effect of Gal-9 mediated through the TIM-3-Gal-9 pathway, Gal-9 may exert its suppressive effect on RA disease activity by modulation of regulatory T (Treg) cells.
authors: Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors: J
authors: J
authors: Lee
authors: J-M
authors: JM
authors: Oh
authors: J W
authors: JW
authors: Hwang
authors: J K
authors: JK
authors: Ahn
authors: E-K
authors: EK
authors: Bae
authors: J
authors: J
authors: Won
authors: E-M
authors: EM
authors: Koh
authors: H-S
authors: HS
authors: Cha
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D037161:Galectins / Q000097:blood / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000097:blood; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins