| First Author | Han JH | Year | 2014 |
| Journal | Eur J Immunol | Volume | 44 |
| Issue | 1 | Pages | 215-26 |
| PubMed ID | 24105635 | Mgi Jnum | J:208660 |
| Mgi Id | MGI:5563887 | Doi | 10.1002/eji.201343714 |
| Citation | Han JH, et al. (2014) Expression of an anti-RNA autoantibody in a mouse model of SLE increases neutrophil and monocyte numbers as well as IFN-I expression. Eur J Immunol 44(1):215-26 |
| abstractText | Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of antinucleic acid autoantibodies, high levels of circulating type I interferon (IFN-I), and an IFN-I-dependent elevated expression of activating FcgammaR. Increases in neutrophils and monocytes are often observed in clinical SLE, but how these contribute to autoantibody and IFN-I production is poorly understood. Here, we analyzed SLE pathogenesis in 564Igi mice, an SLE-model strain carrying gene-targeted heavy and light chain antibody genes encoding an anti-RNA autoantibody in a C57BL/6 background. Similar to human SLE patients, 564Igi mice produce anti-RNA autoantibodies and expanded neutrophil and monocyte populations. These myeloid cells produced IFN-I and exhibit increased FcgammaRIV expression induced via an IFN-I autocrine loop. A direct effect of IFN-I on 56 Igi BM B cells and neutrophils was supported by their upregulation of "IFN-I signature genes". In addition, 564Igi developing B cells showed upregulated TLR7 resulting in IgG2a/2b class switch recombination and autoantibody production. Our results indicate that the production of anti-RNA autoantibody is sufficient to induce an increase of BM, blood, and spleen IFN-I-producing neutrophils, and suggest a mechanism by which autoantibody and IFN-I contribute to SLE by activating B lymphocytes, neutrophils, and monocyte effector cells in vivo. |
