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

Objective:To investigate the function of cytokines,chemokines,and regulatory T cells(Tregs)in the pathogenesis of Type 1 diabeles 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-1βand MCP-1)were detected by enzyme-linked immunosorbent assay.Peripheral blood mononuclear cells(PBMCs)were isolated and culture supernatant of phytohaemagglutinin(PHA)-stimulatcd PBMCs was subjecled to ELISA for levels of cytokines(IL-1α,IL-6,IL-10,IL-12 and TNV-α)in T1DM and control group.Furthermore,flow cytometty 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 andd TNF-αas well as chemokines,such as MIP-1αand MIP-1βin 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-1αand 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 heathy controls(P<0.05).Conclusions:Immune dysfunction.with uprcgulation of inflanunatory factors such as IL-1α.IL-6.TNF-αand MIP-1α.downregulation of IL-10 and Tregs,plays an important role in the pathogenesis of T1DM in children.