010 Skin dysbiosis promotes autoimmune inflammation via neutrophil activation and the IL-23/IL-17 axis

Systemic lupus erythematosus (SLE) is an autoimmune disease, but its etiology not completely understood. Recently, the microbiotas in nasal cavity and gut have been shown to be involved development of SLE, influence skin microbiota still unclear. Here, we demonstrated that NfkbizΔK5 mice treated with Staphylococcus aureus develop SLE-associated autoantibodies glomerulonephritis IgG deposition. Epicutaneous S. application significantly increases staphylococcal colonization reduced expression antimicrobial peptides, which promotes caspase-mediated keratinocyte apoptosis neutrophil activation, inducing IL-23/IL-17 immune response by activating dendritic cells T cells. As a consequence, SLE-like disease. Furthermore, administration anti-IL-23p19 antibody anti-IL-17A antibody, anti-IL-12p40 alleviated systemic response. Our results provide novel murine model for SLE reveal fundamental importance homeostasis.