| First Author | Tsai F | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 12 | Pages | 3753-3773 |
| PubMed ID | 29114065 | Mgi Jnum | J:251967 |
| Mgi Id | MGI:6106511 | Doi | 10.1084/jem.20170479 |
| Citation | Tsai F, et al. (2017) Bim suppresses the development of SLE by limiting myeloid inflammatory responses. J Exp Med 214(12):3753-3773 |
| abstractText | The Bcl-2 family is considered the guardian of the mitochondrial apoptotic pathway. We demonstrate that Bim acts as a molecular rheostat by controlling macrophage function not only in lymphoid organs but also in end organs, thereby preventing the break in tolerance. Mice lacking Bim in myeloid cells (LysM(Cre)Bim(fl/fl)) develop a systemic lupus erythematosus (SLE)-like disease that mirrors aged Bim(-/-) mice, including loss of marginal zone macrophages, splenomegaly, lymphadenopathy, autoantibodies (including anti-DNA IgG), and a type I interferon signature. LysM(Cre)Bim(fl/fl) mice exhibit increased mortality attributed to glomerulonephritis (GN). Moreover, the toll-like receptor signaling adaptor protein TRIF (TIR-domain-containing adapter-inducing interferon-beta) is essential for GN, but not systemic autoimmunity in LysM(Cre)Bim(fl/fl) mice. Bim-deleted kidney macrophages exhibit a novel transcriptional lupus signature that is conserved within the gene expression profiles from whole kidney biopsies of patients with SLE. Collectively, these data suggest that the Bim may be a novel therapeutic target in the treatment of SLE. |
