The expression of FOXP3 and CTLA-4 in peripheral blood mononuclear cells in children with newly onset type 1 diabetes mellitus / 中国小儿急救医学

ABSTRACT

Objective To investigate the expression levels of forkhead transcription factor 3 (FOXP3) and cytotoxic T lymphocyte-associated antigen-4(CTLA-4) in the peripheral blood of children with newly diagnosed type 1 diabetes mellitus(T1DM),and explore their roles in the pathogenesis of T1DM. Methods Fifty children with newly diagnosed T1DM and 30 healthy children( control group) were select-ed. FOXP3 and CTLA-4 mRNA expressions were detected using real-time PCR. Soluble FOXP3 ( sFOXP3 ) and CTLA-4(sCTLA-4) protein levels in the serum were assayed by ELISA,and the levels of diabetes anti-bodies,HbA1C and C-peptide were determined using Western blotting,high performance liquid ion-exchange chromatography,and electrochemiluminescence, respectively. Results The expressions of FOXP3 mRNA and protein in T1DM patients were lower than those in the control group[0. 95 ± 0. 48 vs. 2. 11 ± 0. 79,(6. 27 ± 1. 49) ng/ml vs. (9. 02 ± 2. 37) ng/ml,respectively,both P <0. 01],while the expressions of CTLA-4 mRNA and protein were higher than those in the control group[2. 43 ± 0. 83 vs. 1. 94 ± 0. 84,(77. 88 ± 22. 34) ng/ml vs. (65. 97 ± 12. 11) ng/ml,respectively,both P<0. 01]. In T1DM patients,the expressions of FOXP3 and CTLA-4 genes presented positive correlation with the protein expression( r=0. 758,0. 396, P<0. 05), and FOXP3 protein expression presented correlation with CTLA-4 protein expression ( r =-0. 624,P<0. 05). Conclusion There are abnormal expressions of FOXP3 and CTLA-4 genes as well as their proteins in the peripheral blood of the children with newly diagnosed T1DM,and FOXP3 regulated the expression of CTLA-4 in T regulatory cells,indicating the involvement of immune mechanisms in the devel-opment of T1DM.