title: Increased expression of T cell immunoglobulin- and mucin domain-containing molecule-3 on natural killer cells in atherogenesis.
abstract: OBJECTIVE
  Atherosclerosis (AS) has many features of a chronic inflammatory disease in which both adaptive and innate immune cells play roles. Increasing evidence has demonstrated the impairment of circulating natural killer (NK) cells in atherosclerosis. However, the mechanisms of this impairment remain unclear. We previously reported the suppression of NK cell functions by T cell immunoglobulin- and mucin domain-containing molecule (Tim)-3. Here, we investigated the expression of Tim-3 on NK cells and assessed its possible roles in NK loss during atherogenesis.
  
  
  RESULTS
  Flow cytometry analysis showed increased Tim-3 expression on peripheral NK cells from patients with AS. This increased expression of Tim-3 was significantly related to the levels of serum lipids and inflammation markers, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α, which are risk factors for atherogenesis. We detected decreased peripheral NK cell number in patients with AS. The NK cell number showed significant inverse correlations with Tim-3 expression levels on NK cells and the level of serum TNF-α. Consistently, Tim-3 overexpression reduced NK92 cell number. Blockade of Tim-3 protected NK92 cells from TNF-α-induced cell death. Similar results were obtained with peripheral NK cells from patients with AS.
  
  
  CONCLUSIONS
  To the best of our knowledge, for the first time, the data from our study provide evidence that augmented Tim-3 expression on NK cells plays an important role in NK cell loss in atherosclerosis. The augmented Tim-3 expression on NK cells might be used as an indicator for disease progression.
authors.affiliation: Key Laboratory for Experimental Teratology of Ministry of Education and Institute of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Hou
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Lifen
authors.initials: L
authors.lastname: Gao
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liang
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Gai
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
authors.forename: Faliang
authors.initials: F
authors.lastname: Zhu
authors.forename: Mei
authors.initials: M
authors.lastname: Ni
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wensheng
authors.initials: W
authors.lastname: Sun
authors.forename: Chunhong
authors.initials: C
authors.lastname: Ma
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha