The microRNA miR-181 is a critical cellular metabolic rheostat essential for NKT cell ontogenesis and lymphocyte development and homeostasis.
Immunity
; 38(5): 984-97, 2013 May 23.
Article
em En
| MEDLINE
| ID: mdl-23623381
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
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Linfopoese
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PTEN Fosfo-Hidrolase
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Células T Matadoras Naturais
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article