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Immunity. 2013 May 23;38(5):984-97. doi: 10.1016/j.immuni.2013.02.021. Epub 2013 Apr 25.

The microRNA miR-181 is a critical cellular metabolic rheostat essential for NKT cell ontogenesis and lymphocyte development and homeostasis.

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  • 1Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.

Abstract

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID:
23623381
[PubMed - indexed for MEDLINE]
PMCID:
PMC3738211
Free PMC Article
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