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MiR-142 controls metabolic reprogramming that regulates dendritic cell activation.


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.

SUBMITTER: Sun Y 

PROVIDER: S-EPMC6486330 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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miR-142 controls metabolic reprogramming that regulates dendritic cell activation.

Sun Yaping Y   Oravecz-Wilson Katherine K   Bridges Sydney S   McEachin Richard R   Wu Julia J   Kim Stephanie H SH   Taylor Austin A   Zajac Cynthia C   Fujiwara Hideaki H   Peltier Daniel Christopher DC   Saunders Thomas T   Reddy Pavan P  

The Journal of clinical investigation 20190408 5


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 activat  ...[more]

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