| First Author | Schwarting A | Year | 1998 |
| Journal | J Immunol | Volume | 161 |
| Issue | 1 | Pages | 494-503 |
| PubMed ID | 9647261 | Mgi Jnum | J:110886 |
| Mgi Id | MGI:3641490 | Doi | 10.4049/jimmunol.161.1.494 |
| Citation | Schwarting A, et al. (1998) IFN-gamma receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice. J Immunol 161(1):494-503 |
| abstractText | CSF-1 and TNF-alpha in the kidney of MRL-Fas(lpr) mice are proximal events that precede and promote autoimmune lupus nephritis, while apoptosis of renal parenchymal cells is a feature of advanced human lupus nephritis. In the MRL-Fas(lpr) kidney, infiltrating T cells that secrete IFN-gamma are a hallmark of disease. To examine the impact of IFN-gamma on renal injury in MRL-Fas(lpr) mice, we constructed a IFN-gamma R-deficient strain. In MRL-Fas(lpr) mice lacking IFN-gamma R, circulating and intrarenal CSF-1 were absent, TNF-alpha was markedly reduced, survival was extended, lymphadenopathy and splenomegaly were prevented, and the kidneys remained protected from destruction. Mesangial cells (MC) that were signaled through the IFN-gamma R induced CSF-1 and TNF-alpha in MRL-Fas(lpr) mice. We detected a large number of apoptotic renal parenchymal cells in advanced nephritis and determined that signaling via the IFN-gamma R induces apoptosis of tubular epithelial cells (TEC), but not MC. By comparison, TNF-alpha induces apoptosis in MC, but not TEC, of the MRL-Fas(lpr) strain. Thus, IFN-gamma is directly and indirectly responsible for apoptosis of TEC and MC in MRL-Fas(lpr) mice, respectively. In conclusion, IFN-gamma R signaling is essential for the initiation (CSF-1), acceleration (CSF-1 and TNF-alpha), and apoptotic destruction of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease. |
