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 such as skin, kidneys, bones, and brain and the presence of autoantibodies. Although the cause of SLE is not completely understood, environmental factors, genetic susceptibility, hormone factors, and environmental factors are thought to play essential roles in the pathogenesis of SLE. Among environmental factors, the microbiota are linked to the development of different autoimmune diseases. The microbiota in the nasal cavity and gut are involved in SLE development, but the influence of skin microbiota is still unclear. Here, we demonstrated that epithelial cell-specific IκBζ-deficient (NfkbizΔK5) mice showed spontaneous skin inflammation with increased abundance of Staphylococcus aureus on the skin. When S. aureus was epicutaneously applied on NfkbizΔK5 mice, NfkbizΔK5 mice developed SLE-associated autoantibodies, anti-dsDNA antibodies, anti-Sm antibodies, and glomerulonephritis with IgG deposition. Epicutaneous S. aureus application significantly increased staphylococcal colonization on the skin of NfkbizΔK5 mice with reduced expression of several antimicrobial peptides in the skin. This staphylococcal skin colonization promoted caspase-mediated keratinocyte apoptosis and neutrophil activation, inducing the interleukin-23 (IL-23)/IL-17 immune response by activating dendritic cells and T cells. Furthermore, the subcutaneous administration of anti-IL-23p19 and anti-IL-17A antibodies alleviated the systemic autoimmune response. Together, these findings underscore epithelial-immune cross-talk disturbances caused by skin dysbiosis as an essential mediator inducing autoimmune diseases.

Efficacy and safety of i.v. methylprednisolone pulse therapy for vitiligo: A retrospective study of 58 therapy experiences for 33 vitiligo patients.

Systemic corticosteroid is indicated for vitiligo, especially for generalized and progressive vitiligo. However, no consensus exists yet for the dosages and modalities of systemic corticosteroid treatments for vitiligo. The purpose of this study is to validate the efficacy and safety of i.v. methylprednisolone pulse therapy (IVMP) for patients with progressive generalized vitiligo. We retrospectively reviewed the medical records of vitiligo patients treated in our institute for 10 years between January 2010 and December 2019. Among 525 vitiligo patients treated in 10 years, 33 vitiligo patients (aged, 8-78 years; 18 female and 15 males) received IVMP, a single course of daily 500 mg methylprednisolone application (8 mg/kg/day for children) for 3 consecutive days. We observed that 14 of 25 (56%) achieved stable condition without lesion progression, and 12 of 19 (63%) had more than 25% repigmentation at 6 months after IVMP. A group of Vitiligo Area Scoring Index over 10 included more patients with Vitiligo Disease Activity Score of +3 and +4 disease progression at 6 months after the IVMP. We did not observe any severe adverse events relating to the IVMP procedures. In conclusion, IVMP is a safe and effective treatment for progressive generalized vitiligo.