| First Author | Carvalho-Pinto CE | Year | 2002 |
| Journal | J Immunol | Volume | 169 |
| Issue | 2 | Pages | 1058-67 |
| PubMed ID | 12097414 | Mgi Jnum | J:123834 |
| Mgi Id | MGI:3719744 | Doi | 10.4049/jimmunol.169.2.1058 |
| Citation | Carvalho-Pinto CE, et al. (2002) Autocrine production of IFN-gamma by macrophages controls their recruitment to kidney and the development of glomerulonephritis in MRL/lpr mice. J Immunol 169(2):1058-67 |
| abstractText | Anti-DNA autoantibody production is a key factor in lupus erythematosus development; nonetheless, the link between glomerular anti-DNA autoantibody deposition and glomerulonephritis development is not understood. To study the inflammatory and destructive processes in kidney, we used IFN-gamma(+/-) MRL/lpr mice which produce high anti-DNA Ab levels but are protected from kidney disease. The results showed that defective macrophage recruitment to IFN-gamma(+/-) mouse kidney was not caused by decreased levels of monocyte chemoattractant protein-1, a chemokine that controls macrophage migration to MRL/lpr mouse kidney. To determine which IFN-gamma-producing cell type orchestrates the inflammation pathway in kidney, we transferred IFN-gamma(+/+) monocyte/macrophages or T cells to IFN-gamma(-/-) mice, which do not develop anti-DNA autoantibodies. The data demonstrate that IFN-gamma production by infiltrating macrophages, and not by T cells, is responsible for adhesion molecule up-regulation, macrophage accumulation, and inflammation in kidney, even in the absence of autoantibody deposits. Therefore, in addition to monocyte chemoattractant protein-1, macrophage-produced IFN-gamma controls macrophage migration to kidney; the degree of IFN-gamma production by macrophages also regulates glomerulonephritis development. Our findings establish the level of IFN-gamma secretion by macrophages as a link between anti-DNA autoantibody deposition and glomerulonephritis development, outline the pathway of the inflammatory process, and suggest potential treatment for disease even after autoantibody development. |
