title: Chemokine (C-C motif) ligand 20, a potential biomarker for Graves' disease, is regulated by osteopontin.
abstract: BACKGROUND
  Graves' disease (GD) is a common autoimmune disease involving the thyroid gland. The altered balance of pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of GD. Chemokine (C-C motif) ligand 20 (CCL20) is important for interleukin-17 (IL-17) signal activation and a potent chemoattractant for Th17 cells. Meanwhile, Osteopontin (OPN), a broadly expressed pleiotropic cytokine, has been implicated in GD through inducing Th1-involved response to enhance the production of proinflammatory cytokines and chemokines, but little is known about the role of OPN in regulating CCL20 and IL-17 signaling.
  
  
  OBJECTIVE
  This study sought to explore the possibility of CCL20 level as a biomarker for GD, as well as investigate the role of OPN in regulating CCL20 production.
  
  
  METHODS
  Fifty untreated GD patients, fifteen euthyroid GD patients, twelve TRAb-negative GD patients and thirty-five healthy control donors were recruited. OPN, CCL20 and other clinical GD diagnosis parameters were measured. CD4+T cells were isolated from peripheral blood mononuclear cells (PBMCs) using antibody-coated magnetic beads. Enzyme-linked immune-sorbent assay and quantitative polymerase chain reaction were used to determine CCL20 expression level.
  
  
  RESULTS
  We found that the plasma CCL20 level was enhanced in GD patients and decreased in euthyroid and TRAb-negative GD patients. In addition, CCL20 level correlated with GD clinical diagnostic parameters and plasma OPN level. Moreover, we demonstrated that recombinant OPN and plasma from untreated GD patients increased the expression of CCL20 in CD4+T cells, which could be blocked by OPN antibody. Furthermore, we found that the effect of OPN on CCL20 expression was mediated by β3 integrin receptor, IL-17, NF-κB and MAPK pathways.
  
  
  CONCLUSIONS
  These results demonstrated that CCL20 might serve as a biomarker for GD and suggested the possible role of OPN in induction of CCL20 expression.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Qi
authors.forename: Xinran
authors.initials: X
authors.lastname: Ma
authors.forename: Fengjiao
authors.initials: F
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Dongping
authors.initials: D
authors.lastname: Lin
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.forename: Lingyan
authors.initials: L
authors.lastname: Xu
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D054418:Chemokine CCL20 / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006111:Graves Disease / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D017931:DNA Primers; D012333:RNA, Messenger; D053495:Osteopontin