The MicroRNA miR-181 Is a Critical Cellular Metabolic Rheostat Essential for NKT Cell Ontogenesis and Lymphocyte Development and Homeostasis.
Henao-Mejia, Jorge 1,7; Williams, Adam 1,7; Goff, Loyal A. 2,3,4; Staron, Matthew 1; Licona-Limon, Paula 1; Kaech, Susan M. 1,6; Nakayama, Maki 5; Rinn, John L. 2,3; Flavell, Richard A. 1,6,*
[Article] Immunity. 38(5):984-997, May 2013.

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: 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

(C) 2013Elsevier, Inc.