論文 - 詳細
| RRC ID | 85741 |
|---|---|
| 著者 | Fike AJ, Bricker KN, Gonzalez MV, Maharjan A, Bui T, Nuon K, Emrich SM, Weber JL, Luckenbill SA, Choi NM, Sauteraud R, Liu DJ, Olsen NJ, Caricchio R, Trebak M, Chodisetti SB, Rahman ZSM. |
| タイトル | IRF7 controls spontaneous autoimmune germinal center and plasma cell checkpoints. |
| ジャーナル | J Exp Med |
| Abstract |
How IRF7 promotes autoimmune B cell responses and systemic autoimmunity is unclear. Analysis of spontaneous SLE-prone mice deficient in IRF7 uncovered the IRF7 role in regulating autoimmune germinal center (GC), plasma cell (PC), and autoantibody responses and disease. IRF7, however, was dispensable for foreign antigen-driven GC, PC, and antibody responses. Competitive bone marrow (BM) chimeras highlighted the importance of IRF7 in hematopoietic cells in spontaneous GC and PC differentiation. Single-cell RNAseq of SLE-prone B cells indicated IRF7-mediated B cell differentiation through GC and PC fates. Mechanistic studies revealed that IRF7 promoted B cell differentiation through GC and PC fates by regulating the transcriptome, translation, and metabolism of SLE-prone B cells. Mixed BM chimeras demonstrated a requirement for B cell-intrinsic IRF7 in IgG autoantibody production but not in the regulation of spontaneous GC and PC responses. Altogether, we delineate previously unknown B cell-intrinsic and -extrinsic mechanisms of IRF7-promoted spontaneous GC and PC responses, loss of tolerance, autoantibody production, and SLE development. |
| 巻・号 | 222(7) |
| 公開日 | 2025-7-7 |
| DOI | 10.1084/jem.20231882 |
| PII | 277976 |
| PMID | 40439584 |
| PMC | PMC12121627 |
| MeSH | Animals Autoantibodies / immunology Autoimmunity* / immunology B-Lymphocytes / immunology Cell Differentiation / immunology Germinal Center* / immunology Interferon Regulatory Factor-7* / genetics Interferon Regulatory Factor-7* / immunology Interferon Regulatory Factor-7* / metabolism Lupus Erythematosus, Systemic / genetics Lupus Erythematosus, Systemic / immunology Lupus Erythematosus, Systemic / pathology Mice Mice, Inbred C57BL Mice, Knockout Plasma Cells* / immunology |
| IF | 11.743 |
| 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 | Bluesky |
| 各媒体での言及数の合計 | 39 |
| 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 | RBRC01420 |