| 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
|
| リソース情報 |
| 実験動物マウス |
RBRC00915 |
