| Expansion of CD4+CD25+FOXP3+ regulatory T cells in infants of mothers with type 1 diabetes. | |
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MedLine Citation:
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PMID: 22332874 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Kristiina Luopajärvi; Janne K Nieminen; Jorma Ilonen; Hans K Akerblom; Mikael Knip; Outi Vaarala |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-15 |
Journal Detail:
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Title: Pediatric diabetes Volume: - ISSN: 1399-5448 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100939345 Medline TA: Pediatr Diabetes Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 John Wiley & Sons A/S. |
Affiliation:
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Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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