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miR-142 controls metabolic reprogramming that regulates dendritic cell activation
Yaping Sun, … , Thomas Saunders, Pavan Reddy
Yaping Sun, … , Thomas Saunders, Pavan Reddy
Published May 1, 2019; First published April 8, 2019
Citation Information: J Clin Invest. 2019;129(5):2029-2042. https://doi.org/10.1172/JCI123839.
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Categories: Research Article Hematology Immunology

miR-142 controls metabolic reprogramming that regulates dendritic cell activation

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Abstract

DCs undergo metabolic reprogramming from a predominantly oxidative phosphorylation (OXPHOS) to glycolysis to mount an immunogenic response. The mechanism underpinning the metabolic reprogramming remains elusive. We demonstrate that miRNA-142 (miR-142) is pivotal for this shift in metabolism, which regulates the tolerogenic and immunogenic responses of DCs. In the absence of miR-142, DCs fail to switch from OXPHOS and show reduced production of proinflammatory cytokines and the ability to activate T cells in vitro and in in vivo models of sepsis and alloimmunity. Mechanistic studies demonstrate that miR-142 regulates fatty acid (FA) oxidation, which causes the failure to switch to glycolysis. Loss- and gain-of-function experiments identified carnitine palmitoyltransferase -1a (CPT1a), a key regulator of the FA pathway, as a direct target of miR-142 that is pivotal for the metabolic switch. Thus, our findings show that miR-142 is central to the metabolic reprogramming that specifically favors glycolysis and immunogenic response by DCs.

Authors

Yaping Sun, Katherine Oravecz-Wilson, Sydney Bridges, Richard McEachin, Julia Wu, Stephanie H. Kim, Austin Taylor, Cynthia Zajac, Hideaki Fujiwara, Daniel Christopher Peltier, Thomas Saunders, Pavan Reddy

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