Leukotriene B <sub>4</sub> licenses inflammasome activation to enhance skin host defense
Ana Carolina Guerta Salina, Stephanie L. Brandt, Nathan Klopfenstein, Amondrea Blackman, Júlia Miranda Ribeiro Bazzano, Anderson Sá‐Nunes, Nicole Byers-Glosson, Cláudia Brodskyn, Natália Machado Tavares, Ícaro Bonyek-Silva, Alexandra Ivo de Medeiros, C. Henrique Serezani
Abstract
Significance Production of IL-1β is an essential component of the inflammatory response and host defense. IL-1β secretion is dependent on the activation of an intracellular platform termed inflammasome. The initial inflammatory signals that drive inflammasome activation remains elusive. Here, we show that the bioactive lipid leukotriene B 4 enhances both transcriptional and posttranscriptional programs that activate the inflammasome in vivo and in vitro. We identified critical signaling programs required for inflammasome assembly, IL-1β secretion, and its consequences in skin host defense. Our data also suggest that the prevention of LTB 4 actions might be an important therapeutic strategy to prevent IL-1β–dependent inflammatory diseases by inhibiting both first and second signals necessary for inflammasome activation.