免疫学
免疫系统
炎症
自身抗体
金黄色葡萄球菌
白细胞介素23
抗体
自身免疫性疾病
自身免疫
医学
系统性红斑狼疮
白细胞介素17
生物
疾病
病理
细菌
遗传学
作者
H. Terui,Kenshi Yamasaki,Moyuka Irimada,Mayuko Onodera-Amagai,Naokazu Hatchome,Masato Mizuashi,Ryuta Kawashima,Takao Kawabe,Naoto Ishii,Takaaki Abe,Yoshihide Asano,Setsuya Aiba
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2022-10-28
卷期号:7 (76)
被引量:29
标识
DOI:10.1126/sciimmunol.abm9811
摘要
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 ( Nfkbiz ΔK5 ) mice showed spontaneous skin inflammation with increased abundance of Staphylococcus aureus on the skin. When S. aureus was epicutaneously applied on Nfkbiz ΔK5 mice, Nfkbiz ΔK5 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 Nfkbiz ΔK5 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.
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