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 |
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| description | 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. |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0066282</identifier><identifier>PMID: 23741528</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Autoimmune diseases ; Biology ; Cancer ; Cell culture ; Cytokines ; Diabetes ; Experiments ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; Foxp3 protein ; Gene Deletion ; Gene Expression Regulation ; Genes, Lethal ; Homeostasis ; Immunology ; Immunoregulation ; Liver - metabolism ; Liver - pathology ; Lung - metabolism ; Lung - pathology ; Lymphatic system ; Lymphocytes ; Lymphocytes T ; Medical research ; Medicine ; Mice ; Mice, Transgenic ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Protein Stability ; RNA-Binding Proteins - genetics ; RNA-Binding Proteins - metabolism ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism ; Transcription factors</subject><ispartof>PloS one, 2013-05, Vol.8 (5), p.e66282</ispartof><rights>2013 Jeker et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</description><subject>Animals</subject><subject>Autoimmune diseases</subject><subject>Biology</subject><subject>Cancer</subject><subject>Cell culture</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Experiments</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Foxp3 protein</subject><subject>Gene Deletion</subject><subject>Gene Expression Regulation</subject><subject>Genes, Lethal</subject><subject>Homeostasis</subject><subject>Immunology</subject><subject>Immunoregulation</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Lymphatic system</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>MicroRNAs</subject><subject>MicroRNAs - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23741528</pmid><doi>10.1371/journal.pone.0066282</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Autoimmune diseases Biology Cancer Cell culture Cytokines Diabetes Experiments Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism Foxp3 protein Gene Deletion Gene Expression Regulation Genes, Lethal Homeostasis Immunology Immunoregulation Liver - metabolism Liver - pathology Lung - metabolism Lung - pathology Lymphatic system Lymphocytes Lymphocytes T Medical research Medicine Mice Mice, Transgenic MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miRNA Protein Stability RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism Transcription factors |
| title | DGCR8-mediated production of canonical microRNAs is critical for regulatory T cell function and stability |
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