DGCR8-mediated production of canonical microRNAs is critical for regulatory T cell function and stability

Regulatory T cells (Treg) are integral for immune homeostasis. Here we demonstrate that canonical microRNAs (miRNAs) are required for Treg function because mice with DGCR8-deficient Treg cells spontaneously develop a scurfy-like disease. Using genetic lineage marking we show that absence of miRNAs l...

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Veröffentlicht in:PloS one 2013-05, Vol.8 (5), p.e66282
Hauptverfasser: Jeker, Lukas T, Zhou, Xuyu, Blelloch, Robert, Bluestone, Jeffrey A
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Sprache:eng
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Zusammenfassung:Regulatory T cells (Treg) are integral for immune homeostasis. Here we demonstrate that canonical microRNAs (miRNAs) are required for Treg function because mice with DGCR8-deficient Treg cells spontaneously develop a scurfy-like disease. Using genetic lineage marking we show that absence of miRNAs leads to reduced FoxP3 expression in Treg cells in vivo. In vitro culture of purified DGCR8-deficient Treg leads to a loss of FoxP3 expression. We conclude that canonical miRNAs are essential to maintain stable FoxP3 expression and Treg function. Thus, signals interfering with miRNA homeostasis might contribute to autoimmune diseases.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0066282