Role of immune dysfunction in pathogenesis of type 1 diabetes mellitus in children

Abstract

Objectives: 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.

Keywords: Chemokine; Cytokine; Regulatory T cell; Type 1 diabetes mellitus.