Leukotriene B ₄ licenses inflammasome activation to enhance skin host defense

This is the authors' abstract. We don't add key points for this paper.

The initial production of inflammatory mediators dictates host defense as well as tissue injury. Inflammasome activation is a constituent of the inflammatory response by recognizing pathogen and host-derived products and eliciting the production of IL-1β, IL-18 as well as inducing a type of inflammatory cell death termed “pyroptosis”. Leukotriene B 4 (LTB 4 ) is a lipid mediator produced quickly (seconds to minutes) by phagocytes and induces chemotaxis, enhances cytokine/chemokine production, and enhances antimicrobial effector functions. Whether LTB 4 directly activates the inflammasome is not well understood. Our data show that endogenously produced LTB 4 is required for the expression of pro-IL-1β in vivo and in vitro and enhances inflammasome assembly. Furthermore, LTB 4 -mediated Bruton’s tyrosine kinase (BTK) activation is required for inflammasome assembly in vivo as well for IL-1β-enhanced skin host defense. Together, these data unveil a new role for LTB 4 in enhancing the expression and assembly of inflammasome components and suggest that while blocking LTB 4 actions could be a promising therapeutic strategy to prevent inflammasome-mediated diseases, exogenous LTB 4 can be used as an adjuvant to boost inflammasome-dependent host defense.