The MicroRNA miR-181 Is a Critical Cellular Metabolic Rheostat Essential for NKT Cell Ontogenesis and Lymphocyte Development and Homeostasis
Regulation of metabolic pathways in the immune system provides a mechanism to actively control cellular function, growth, proliferation, and survival. Here, we report that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early N...
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| Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2013-05, Vol.38 (5), p.984-997 |
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| container_title | Immunity (Cambridge, Mass.) |
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| creator | Henao-Mejia, Jorge Williams, Adam Goff, Loyal A. Staron, Matthew Licona-Limón, Paula Kaech, Susan M. Nakayama, Maki Rinn, John L. Flavell, Richard A. |
| description | Regulation of metabolic pathways in the immune system provides a mechanism to actively control cellular function, growth, proliferation, and survival. Here, we report that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early NKT cell development. As a result, miR-181-deficient mice showed a complete absence of mature NKT cells in the thymus and periphery. Mechanistically, miR-181 modulated expression of the phosphatase PTEN to control PI3K signaling, which was a primary stimulus for anabolic metabolism in immune cells. Thus miR-181-deficient mice also showed severe defects in lymphoid development and T cell homeostasis associated with impaired PI3K signaling. These results uncover miR-181 as essential for NKT cell development and establish this family of miRNAs as central regulators of PI3K signaling and global metabolic fitness during development and homeostasis.
•miR-181 regulates cellular metabolic fitness required for robust proliferation•miR-181 is essential for NKT cell development•miR-181 is a PTEN rheostat and a central regulator of the PI3K pathway in vivo•miR-181 is a critical regulator of lymphocyte development and homeostasis |
| doi_str_mv | 10.1016/j.immuni.2013.02.021 |
| format | Article |
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Here, we report that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early NKT cell development. As a result, miR-181-deficient mice showed a complete absence of mature NKT cells in the thymus and periphery. Mechanistically, miR-181 modulated expression of the phosphatase PTEN to control PI3K signaling, which was a primary stimulus for anabolic metabolism in immune cells. Thus miR-181-deficient mice also showed severe defects in lymphoid development and T cell homeostasis associated with impaired PI3K signaling. These results uncover miR-181 as essential for NKT cell development and establish this family of miRNAs as central regulators of PI3K signaling and global metabolic fitness during development and homeostasis.
•miR-181 regulates cellular metabolic fitness required for robust proliferation•miR-181 is essential for NKT cell development•miR-181 is a PTEN rheostat and a central regulator of the PI3K pathway in vivo•miR-181 is a critical regulator of lymphocyte development and homeostasis</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23623381</pmid><doi>10.1016/j.immuni.2013.02.021</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Cell Differentiation Chemokine CXCL12 - metabolism Down-Regulation Homeostasis Kinases Lymphocytes - metabolism Lymphopoiesis - genetics Metabolism Mice MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Natural Killer T-Cells - metabolism Phosphatase Phosphatidylinositol 3-Kinases - metabolism PTEN Phosphohydrolase - metabolism Rodents Signal Transduction - genetics Statistical analysis T cell receptors |
| title | The MicroRNA miR-181 Is a Critical Cellular Metabolic Rheostat Essential for NKT Cell Ontogenesis and Lymphocyte Development and Homeostasis |
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