BACKGROUND: Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers. OBJECTIVE: To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D. SUBJECTS AND METHODS: Cord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with human insulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)-10, and transforming growth factor (TGF)-β was measured by real-time reverse transcription polymerase chain reaction. RESULTS: The percentage of FOXP3+ cells in CD4+CD25(high) cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25(high) cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL-10, and TGF-β transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease-related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin-stimulated CBMCs (p = 0.007 and p = 0.014). CONCLUSIONS: We suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes.
RCT Entities:
BACKGROUND: Reduced risk for type 1 diabetes (T1D) has been reported in the offspring of mothers with T1D when compared with children of affected fathers. OBJECTIVE: To evaluate the hypothesis that exposure of the offspring to maternal insulin therapy induces regulatory mechanisms in utero, we compared the FOXP3 expressing regulatory T cells in cord blood (CB) of infants born to mothers with or without T1D. SUBJECTS AND METHODS: Cord blood mononuclear cells (CBMCs) from 20 infants with maternal T1D and from 20 infants with an unaffected mother were analyzed for the numbers of CD4+CD25+FOXP3+ cells ex vivo and after in vitro stimulation with humaninsulin by flow cytometry. The mRNA expression of FOXP3, NFATc2, STIM1, interleukin (IL)-10, and transforming growth factor (TGF)-β was measured by real-time reverse transcription polymerase chain reaction. RESULTS: The percentage of FOXP3+ cells in CD4+CD25(high) cells was higher in the CB of the infants with maternal T1D when compared with the infants of unaffected mothers (p = 0.023). After in vitro insulin stimulation an increase in the percentage of FOXP3+ cells in CD4+CD25(high) cells (p = 0.0002) as well as upregulation of FOXP3, NFATc2, STIM1, IL-10, and TGF-β transcripts in CBMCs (p < 0.013 for all; Wilcoxon test) was observed only in the offspring of mothers with T1D, in whom the disease-related PTPN22 allele was associated with reduced STIM1 and NFATc2 response in insulin-stimulated CBMCs (p = 0.007 and p = 0.014). CONCLUSIONS: We suggest that maternal insulin treatment induces expansion of regulatory T cells in the fetus, which might contribute to the lower risk of diabetes in children with maternal vs. paternal diabetes.
Authors: U Di Mario; F Fallucca; P Gargiulo; C Tiberti; A Scardellato; P Arduini; A Pachi'; D Andreani Journal: Diabetologia Date: 1984-07 Impact factor: 10.122
Authors: Marika Kukko; Suvi M Virtanen; Anna Toivonen; Satu Simell; Sari Korhonen; Jorma Ilonen; Olli Simel; Mikael Knip Journal: Diabetes Care Date: 2004-03 Impact factor: 19.112
Authors: Adebola Matthew Giwa; Rizwan Ahmed; Zahra Omidian; Neha Majety; Kagan Ege Karakus; Sarah M Omer; Thomas Donner; Abdel Rahim A Hamad Journal: World J Diabetes Date: 2020-01-15