0000000000342058
AUTHOR
Yasunori Iwata
IL-34–Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL-Faslpr Mice
Background In people with SLE and in the MRL- Fas lpr lupus mouse model, macrophages and autoantibodies are central to lupus nephritis. IL-34 mediates macrophage survival and proliferation, is expressed by tubular epithelial cells (TECs), and binds to the cFMS receptor on macrophages and to a newly identified second receptor, PTPRZ. Methods To investigate whether IL-34–dependent intrarenal and systemic mechanisms promote lupus nephritis, we compared lupus nephritis and systemic illness in MRL- Fas lpr mice expressing IL-34 and IL-34 knockout (KO) MRL- Fas lpr mice. We also assessed expression of IL-34 and the cFMS and PTPRZ receptors in patients with lupus nephritis. Results Intrarenal IL-3…
CSF-1 signals directly to renal tubular epithelial cells to mediate repair in mice
金沢大学医薬保健研究域医学系
Circulating CSF-1 Promotes Monocyte and Macrophage Phenotypes that Enhance Lupus Nephritis
Macrophages mediate kidney disease and are prominent in a mouse model (MRL- Fas lpr ) of lupus nephritis. Colony stimulating factor-1 (CSF-1) is the primary growth factor for macrophages, and CSF-1 deficiency protects MRL- Fas lpr mice from kidney disease and systemic illness. Whether this renoprotection derives from a reduction of macrophages and whether systemic CSF-1, as opposed to intrarenal CSF-1, promotes macrophage-dependent lupus nephritis remain unclear. Here, we found that increasing systemic CSF-1 hastened the onset of lupus nephritis in MRL- Fas lpr mice. Using mutant MRL- Fas lpr strains that express high, moderate, or no systemic CSF-1, we detected a much higher tempo of kidne…