title: Aberrant T cell differentiation in the absence of Dicer.
abstract: Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and vertebrates. To test the requirement for Dicer in cell-lineage decisions in a mammalian organism, we have generated a conditional allele of dicer-1 (dcr-1) in the mouse. Specific deletion of dcr-1 in the T cell lineage resulted in impaired T cell development and aberrant T helper cell differentiation and cytokine production. A severe block in peripheral CD8(+) T cell development was observed upon dcr-1 deletion in the thymus. However, Dicer-deficient CD4(+) T cells, although reduced in numbers, were viable and could be analyzed further. These cells were defective in microRNA processing, and upon stimulation they proliferated poorly and underwent increased apoptosis. Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-gamma, the hallmark effector cytokine of the Th1 lineage.
authors: The CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Stefan A
authors: SA
authors: Muljo
authors: K Mark
authors: KM
authors: Ansel
authors: Chryssa
authors: C
authors: Kanellopoulou
authors: David M
authors: DM
authors: Livingston
authors: Anjana
authors: A
authors: Rao
authors: Klaus
authors: K
authors: Rajewsky
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D007371:Interferon-gamma; D051379:Mice; D018345:Mice, Knockout; D034622:RNA Interference / Q000276:immunology*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics / Q000276:immunology; D043244:Ribonuclease III / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D007371:Interferon-gamma; D043244:Ribonuclease III