論文 - 詳細
| RRC ID | 5462 |
|---|---|
| 著者 | Thibault DL, Chu AD, Graham KL, Balboni I, Lee LY, Kohlmoos C, Landrigan A, Higgins JP, Tibshirani R, Utz PJ. |
| タイトル | IRF9 and STAT1 are required for IgG autoantibody production and B cell expression of TLR7 in mice. |
| ジャーナル | J Clin Invest |
| Abstract |
A hallmark of SLE is the production of high-titer, high-affinity, isotype-switched IgG autoantibodies directed against nucleic acid-associated antigens. Several studies have established a role for both type I IFN (IFN-I) and the activation of TLRs by nucleic acid-associated autoantigens in the pathogenesis of this disease. Here, we demonstrate that 2 IFN-I signaling molecules, IFN regulatory factor 9 (IRF9) and STAT1, were required for the production of IgG autoantibodies in the pristane-induced mouse model of SLE. In addition, levels of IgM autoantibodies were increased in pristane-treated Irf9 -/- mice, suggesting that IRF9 plays a role in isotype switching in response to self antigens. Upregulation of TLR7 by IFN-alpha was greatly reduced in Irf9 -/- and Stat1 -/- B cells. Irf9 -/- B cells were incapable of being activated through TLR7, and Stat1 -/- B cells were impaired in activation through both TLR7 and TLR9. These data may reveal a novel role for IFN-I signaling molecules in both TLR-specific B cell responses and production of IgG autoantibodies directed against nucleic acid-associated autoantigens. Our results suggest that IFN-I is upstream of TLR signaling in the activation of autoreactive B cells in SLE. |
| 巻・号 | 118(4) |
| ページ | 1417-26 |
| 公開日 | 2008-4-1 |
| DOI | 10.1172/JCI30065 |
| PMID | 18340381 |
| PMC | PMC2267033 |
| MeSH | Adjuvants, Immunologic Animals Autoantibodies / immunology* B-Lymphocytes / immunology* B-Lymphocytes / metabolism* Gene Expression Profiling Immunoglobulin G / biosynthesis Immunoglobulin G / classification Immunoglobulin G / immunology* Interferon-Stimulated Gene Factor 3, gamma Subunit / deficiency Interferon-Stimulated Gene Factor 3, gamma Subunit / genetics Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism* Kidney Diseases / genetics Kidney Diseases / metabolism Kidney Diseases / pathology Mice Mice, Inbred BALB C Mice, Knockout Plasmacytoma / genetics Plasmacytoma / metabolism Plasmacytoma / pathology Protein Binding STAT1 Transcription Factor / deficiency STAT1 Transcription Factor / genetics STAT1 Transcription Factor / metabolism* Toll-Like Receptor 7 / metabolism* Toll-Like Receptor 9 / metabolism |
| IF | 11.864 |
| 引用数 | 62 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | F1000Research |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00915 |