title: Integrative analysis of mRNA and miRNA array data reveals the suppression of retinoic acid pathway in regulatory T cells of Graves' disease.
abstract: BACKGROUND
  It is well known that regulatory T cells (Tregs) are abnormal in Graves' disease (GD) and play crucial roles in the breakdown of immune tolerance and GD development. However, there are controversies about whether the quantity and/or function of Tregs is aberrant in GD. The molecular mechanism of Tregs abnormality and its effects on GD development was still unclear, until now.
  
  
  OBJECTIVE
  MiRNAs play important roles in the function and development of the immune system including Tregs. To reveal the Tregs abnormality and its molecular mechanism in GD, we systematically studied the quantity and immunosuppressive function as well as the differential expression profiles of miRNA and mRNA of Tregs in newly diagnosed patients with GD using TaqMan miRNA array and mRNA microarray.
  
  
  RESULTS
  Our results showed that the quantity and immunosuppressive function of Tregs in initial patients with GD was significantly decreased. More importantly, the retinoic acid (RA) pathway was markedly suppressed and its agonist, all-trans retinoic acid, could notably improve the quantity and immunosuppressive function of Tregs from patients with GD in vitro. In addition, many other pathways including protein ubiquitination and circadian rhythm were also significantly regulated in Tregs of GD.
  
  
  CONCLUSIONS
  This integrative study first revealed the expression profiles of mRNA/miRNA in Tregs of initial GD and RA pathway might play important roles in GD development. Our results implied that all-trans RA, which had been used for a long time in the clinical setting, had potential value in the treatment of GD and was worthy of additional study.
authors.affiliation: Division of Endocrinology and Metabolism (Z.W., J.J.Z., R.R.Z., T.L., W.C.L.) and Division of Rehabilitation Medicine (X.H.F.), Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, China; National Glycoengineering Research Center (X.B.), Shandong University, Jinan 250100, China; Central Research Laboratory (Q.Y.Z.), The Second Hospital of Shandong University, Jinan 250033, China; and Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Ministry of Public Health (Q.Y.Z., Z.W.L), Qilu Hospital, Shandong University, Jinan 250100, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Fan
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zhang
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Lin
authors.forename: Ting
authors.initials: T
authors.lastname: Lu
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.forename: Wenchao
authors.initials: W
authors.lastname: Li
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
authors.forename: Qunye
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000328:Adult; D005260:Female; D006111:Graves Disease / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory; D014212:Tretinoin / Q000819:agonists / Q000097:blood
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D014212:Tretinoin