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