G-CSF Treatment Can Improve Lupus Nephritis
Granulocyte-colony stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. Its application and benefits in the treatment of systemic lupus erythematosus (SLE) are still doubtful while opinions and study results are controversial.
A recent study shows however that G-CSF treatment can ameliorate lupus nephritis in through the preferential expansion of CD4+CD25+Foxp3+ Tregs as well as myeloid-derived suppressor cells (MDSCs). Authors have come to the conclusion that G-CSF has a therapeutic potential for lupus nephritis.
Study design
It should be noted that the study is using female mice that spontaneously develop a disease closely resembling human SLE. NZB/W F1 female mice were treated with G-CSF or phosphate-buffered saline for 5 consecutive days every week from 24 weeks of age, and were analyzed at 36 weeks of age.
Results
- G-CSF treatment decreased proteinuria and serum anti-dsDNA, increased serum complement component 3 (C3), and attenuated renal tissue injury including deposition of IgG and C3.
- G-CSF treatment also decreased serum levels of BUN and creatinine, and ultimately decreased mortality of NZB/W F1 mice.
- G-CSF treatment induced expansion of CD4+CD25+Foxp3+ Tregs, with decreased renal infiltration of T cells, B cells, inflammatory granulocytes and monocytes in both kidneys and spleen.
- G-CSF treatment also decreased expression levels of MCP-1, IL-6, IL-2, and IL-10 in renal tissues as well as serum levels of MCP-1, IL-6, TNF-α, IL-10, and IL-17.
- When Tregs were depleted by PC61 treatment, G-CSF-mediated protective effects on lupus nephritis were abrogated
Why is this important?
Systemic lupus erythematosus is a chronic, multisystem, inflammatory, autoimmune disease, occurring mostly in young women.Renal disease can develop at any time and may be the only manifestation of SLE. It can be mild and asymptomatic or progressive and even fatal.
Reference
Yan, Ji-Jing, et al. "Granulocyte colony-stimulating factor treatment ameliorates lupus nephritis through the expansion of regulatory T cells." BMC Nephrology 17.1 (2016): 175.