title: Role of immune dysfunction in pathogenesis of type 1 diabetes mellitus in children.
abstract: OBJECTIVE
  To investigate the function of cytokines, chemokines, and regulatory T cells (Tregs) in the pathogenesis of type 1 diabetes mellitus (T1DM) in children.
  
  
  METHODS
  A total of 35 children with T1DM and 30 healthy controls were enrolled in this study. Levels of serum cytokines (IL-1α, IL-6, IL-10, IL-12, and TNF-α) and chemokines (MIP-1α, MIP-1α and MCP-1) were detected by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) were isolated and culture supernatant of phytohaemagglutinin (PHA)-stimulated PBMCs was subjected to ELISA for levels of cytokines (IL-1α, IL-6, IL-10, IL-12 and TNF-α) in T1DM and control group. Furthermore, flow cytometry was used to determine the percentage of Tregs in PBMCs of two groups.
  
  
  RESULTS
  Levels of serum cytokines including IL-1α, IL-6, IL-10 and TNF-α as well as chemokines, such as MIP-1α and MIP-1α in children with T1DM children were significantly higher than those in healthy controls (P<0.05, respectively). PBMCs with PHA stimulation in T1DM group secreted more IL-1α and TNF-α (P<0.05, respectively), but less IL-10 (P<0.05), as compared with control group. Furthermore, the proportion of CD4(+), CD25(+), Foxp3(+), Tregs in PBMCs isolated from children with T1DM was obviously lower than those in healthy controls (P<0.05).
  
  
  CONCLUSIONS
  Immune dysfunction, with upregulation of inflammatory factors such as IL-1α, IL-6, TNF-α and MIP-1α, downregulation of IL-10 and Tregs, plays an important role in the pathogenesis of T1DM in children.
authors.affiliation: Department of Pediatrics, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China.
authors.forename: Jin-Shui
authors.initials: JS
authors.lastname: He
authors.affiliation: Department of Pediatrics, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China.
authors.forename: Pu-Song
authors.initials: PS
authors.lastname: Xie
authors.affiliation: Basic Medical Science, Fujian Medical University, Fuzhou, 350108, China. Electronic address: luodaoshu3213@163.com.
authors.forename: Dao-Shu
authors.initials: DS
authors.lastname: Luo
authors.affiliation: Department of endocrinology, Children's Hospital of Fudan University, Shanghai, 200032, China.
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China.
authors.forename: Yu-Gui
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, China.
authors.forename: Fu-Xing
authors.initials: FX
authors.lastname: Liu
keywords: Chemokine; Cytokine; Regulatory T cell; Type 1 diabetes mellitus