title: Tim-3 suppression combined with TLR3 activation enhances antiviral immune response in patients with chronic HCV infection.
abstract: OBJECTIVE
  To investigate the regulation mechanism of T cell immunoglobulin and mucin domain-3 (Tim-3) combined with toll-like receptor 3 (TLR3) or TLR4 on antiviral immune and inflammatory response in patients with chronic hepatitis C virus (HCV) infection.
  
  
  METHODS
  Patients with chronic HCV infection and healthy control subjects were recruited. Patients received interferon (IFN)-α based therapy. Plasma galectin-9 (Gal-9) was quantitated. Peripheral blood mononuclear cells (PBMCs) were cultured with TLR3 or TLR4 agonists, alone or in combination with Tim-3 antagonist. Levels of IFN-α, TNF-α, and 2'-5' oligoadenylate synthetase (2'-5'OAS), myxovirus resistance protein A (MxA) and suppressor of cytokine 1 (SOCS1) RNA in PBMC cultures were evaluated.
  
  
  RESULTS
  Plasma Gal-9 levels were increased in patients (n = 52) compared with controls (n = 20) and significantly declined at treatment week 12 and 24 weeks post-treatment. IFN-α, 2'-5'OAS, MxA, TNF-α and SOCS1 were upregulated by TLR3 and TLR4 agonists. TNF-α and SOCS1 levels were suppressed by the addition of Tim-3 antagonist.
  
  
  CONCLUSIONS
  Tim-3 blockade in combination with TLR activation induces the expression of antiviral molecules without a significant increase in TNF-α or SOCS1.
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China nanyuemin@163.com.
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Nan
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Su
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Niu
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Su-Xian
authors.initials: SX
authors.lastname: Zhao
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yu-Guo
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Rong-Qi
authors.initials: RQ
authors.lastname: Wang
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Ling-Bo
authors.initials: LB
authors.lastname: Kong
authors.affiliation: Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Infectious Disease, the Fifth Hospital of Shijiazhuang City, Shijiazhuang, China.
authors.forename: Huan-Wei
authors.initials: HW
authors.lastname: Zheng
authors.affiliation: Department of Liver Disease, Bethune International Peace Hospital, Shijiazhuang, China.
authors.forename: Dian-Xing
authors.initials: DX
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000378:metabolism*; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D037161:Galectins / Q000097:blood; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007155:Immunologic Factors / Q000097:blood; D008297:Male; D008875:Middle Aged; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D007155:Immunologic Factors; C105032:LGALS9 protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3
keywords: Galectin-9; Hepatitis C virus; T cell immunoglobulin and mucin domain-3; antiviral immunological response; peripheral blood mononuclear cells; toll-like receptors