TY - JOUR AU - Sun, Yaping AU - Oravecz-Wilson, Katherine AU - Bridges, Sydney AU - McEachin, Richard AU - Wu, Julia AU - Kim, Stephanie H. AU - Taylor, Austin AU - Zajac, Cynthia AU - Fujiwara, Hideaki AU - Peltier, Daniel Christopher AU - Saunders, Thomas AU - Reddy, Pavan T1 - miR-142 controls metabolic reprogramming that regulates dendritic cell activation PY - 2019/05/01/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI123839 VL - 129 IS - 5 UR - https://doi.org/10.1172/JCI123839 SP - 2029 EP - 2042 PB - The American Society for Clinical Investigation ER -