0000000000255847
AUTHOR
Amrendra Kumar Ajay
TD-09 IL-34 promotes macrophage-mediated lupus nephritis in MRL-Faslpr mice
Background Nephritis is the major cause of mortality and morbidity in patients with lupus. Macrophages (Mo) are central to kidney destruction in lupus-prone mice and patients. CSF-1, and the newly identified IL-34, mediate Mo survival and proliferation. However, IL-34 and CSF-1 differ during development and disease. While CSF-1 and IL-34 share the CSF-1 receptor (cFMS), expressed by Mo, IL-34 binds to a second receptor, Protein-Tyrosine Phosphatase ζ (PTPRZ) in inflamed kidneys. Intra-renal IL-34, cFMS, and PTPRZ are increased during the progression of lupus nephritis in MRL-Faslpr mice. Therefore, we hypothesized that IL-34 is a potential therapeutic target for lupus nephritis. Methods and…
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…