Cathelicidin LL-37 Ignites Primed NLRP3 Inflammasomes in Rosacea

Microbes and commensal mites contribute to the development of inflammation and neurovascular dysregulation in rosacea. Cathelicidin family proteins are epithelial antimicrobial peptides expressed in higher-order mammals. In humans, mature LL-37 is cleaved from its precursor in response to microbial infection, UV light, and injury. In their new article in the Journal of Investigative Dermatology, Yoon et al. expand on existing evidence supporting LL-37 proinflammatory activity in lipopolysaccharide (LPS)- and UV-primed models of rosacea. They show in vitro that LL-37 promotes NLRP3-mediated inflammasome activation through lysosomal destabilization in the presence of LPS and that the injection of LL-37 in vivo leads to skin inflammation that is abrogated by direct NLRP3 inhibition and homozygous knockout in a murine model.