title: DGCR8-mediated production of canonical microRNAs is critical for regulatory T cell function and stability.
abstract: 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.
authors.affiliation: Diabetes Center and the Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Lukas T
authors.initials: LT
authors.lastname: Jeker
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zhou
authors.forename: Robert
authors.initials: R
authors.lastname: Blelloch
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005804:Genes, Lethal; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D055550:Protein Stability; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: C474044:Dgcr8 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D035683:MicroRNAs; C529101:Mirn150 microRNA, mouse; D016601:RNA-Binding Proteins