Circulating CSF-1 promotes monocyte and macrophage phenotypes that enhance lupus nephritis

Julia Menke, Whitney A. Rabacal, Katelyn T. Byrne, Yasunori Iwata, Melvin M. Schwartz, E. Richard Stanley, Andreas Schwarting, Vicki Rubin Kelley

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Macrophages mediate kidney disease and are prominent in a mouse model (MRL-Faslpr) of lupus nephritis. Colony stimulating factor-1 (CSF-1) is the primary growth factor for macrophages, and CSF-1 deficiency protects MRL-Faslpr 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-Faslpr mice. Using mutant MRL-Faslpr strains that express high, moderate, or no systemic CSF-1, we detected a much higher tempo of kidney disease in mice with the highest level of CSF-1. Furthermore, we uncovered a multistep CSF-1-dependent systemic mechanism central to lupus nephritis. CSF-1 heightened monocyte proliferation in the bone marrow (SSClowCD11b+), and these monocytes subsequently seeded the circulation. Systemic CSF-1 skewed the frequency of monocytes toward "inflammatory" (SSClowCD11b +Ly6Chigh) and activated populations that homed to sites of inflammation, resulting in a more rapid accumulation of intrarenal macrophages (CD11b+CSF-1R+ or CD68+) that induced apoptosis of tubular epithelial cells, damaging the kidney. In humans, we found increased levels of CSF-1 in the serum, urine, and kidneys of patients with lupus compared with healthy controls. Furthermore, serum and urine CSF-1 levels correlated with lupus activity, and intrarenal CSF-1 expression correlated with the histopathology activity index of lupus nephritis. Taken together, circulating CSF-1 is a potential therapeutic target for lupus nephritis.

Original languageEnglish (US)
Pages (from-to)2581-2592
Number of pages12
JournalJournal of the American Society of Nephrology
Issue number12
StatePublished - Dec 1 2009

ASJC Scopus subject areas

  • Nephrology


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