論文 - 詳細
| RRC ID | 73026 |
|---|---|
| 著者 | Terui H, Yamasaki K, Wada-Irimada M, Onodera-Amagai M, Hatchome N, Mizuashi M, Yamashita R, Kawabe T, Ishii N, Abe T, Asano Y, Aiba S. |
| タイトル | Staphylococcus aureus skin colonization promotes SLE-like autoimmune inflammation via neutrophil activation and the IL-23/IL-17 axis. |
| ジャーナル | Sci Immunol |
| Abstract |
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. |
| 巻・号 | 7(76) |
| ページ | eabm9811 |
| 公開日 | 2022-10-28 |
| DOI | 10.1126/sciimmunol.abm9811 |
| PMID | 36306369 |
| MeSH | Adaptor Proteins, Signal Transducing Animals Autoantibodies Inflammation Interleukin-23 Lupus Erythematosus, Systemic* Mice Neutrophil Activation Staphylococcal Infections* Staphylococcus aureus |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 148 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 実験動物マウス | RBRC06410 |