001 Staphylococcus aureus skin colonization promotes SLE-like autoimmune inflammation via neutrophil activation and the IL-23/IL-17 axis

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by inflammation of various organs with unknown etiology. Environmental factors and genetic are thought to play essential roles in the pathogenesis SLE. The microbiota nasal cavity gut involved SLE development, but influence skin still unclear. Here, we demonstrated that epithelial cell-specific IκBζ-deficient (NfkbizΔK5) mice showed spontaneous increased abundance Staphylococcus aureus. With epicutaneous S. aureus application, NfkbizΔK5 developed SLE-associated autoantibodies glomerulonephritis IgG deposition. Epicutaneous application significantly staphylococcal colonization on reduced expression several antimicrobial peptides skin. This promoted caspase-mediated keratinocyte apoptosis neutrophil activation, inducing IL-23/IL-17 immune response activating dendritic cells T cells. Furthermore, subcutaneous administration anti-IL-23p19 anti-IL-17A antibodies alleviated systemic response. Taken together, these findings underscore epithelial-immune crosstalk disturbances caused dysbiosis as mediator diseases.