Granulocyte colony-stimulating factor treatment ameliorates lupus nephritis through the expansion of regulatory T cells

Abstract

BackgroundGranulocyte colony-stimulating factor (G-CSF) can induce regulatory T cells (Tregs) as well as myeloid-derived suppressor cells (MDSCs). Despite the immune modulatory effects of G-CSF, results of G-CSF treatment in systemic lupus erythematosus are still controversial. We therefore investigated whether G-CSF can ameliorate lupus nephritis and studied the underlying mechanisms.MethodsNZB/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.ResultsG-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.ConclusionsG-CSF treatment ameliorated lupus nephritis through the preferential expansion of CD4+CD25+Foxp3+ Tregs. Therefore, G-CSF has a therapeutic potential for lupus nephritis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0380-x) contains supplementary material, which is available to authorized users.

The roles of CSFs on the functional polarization of tumor‐associated macrophages

“…The fraction of CD34 + monocytes in blood inversely correlates with the incidence of acute graft‐versus‐host disease in humans . In mice, G‐CSF also mobilizes murine multipotent CD34 + progenitors which favor Treg cell expansion, thereby preventing spontaneous type I diabetes and ameliorating lupus nephritis .…”

Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis

“…Recently, new evidence revealed that MDSCs play a crucial role in the regulation of LN. The granulocyte colony stimulating factor treatment ameliorated LN through reducing the number of G-MDSCs and M-MDSCs and promoting the preferential expansion of CD4 + CD25 + Foxp3 + Tregs in the spleen and kidney of NZB/W F1 female mice ( 12 ). Consistent with these results, in our previous study, the proportion of MDSCs in the kidney gradually increased along with the progression of SLE in MRL/lpr lupus-prone mice ( 13 ).…”

Mobilization of Hematopoietic Progenitor Cells with Standard- or Reduced-Dose Filgrastim after Vinorelbine in Multiple Myeloma Patients: A Randomized Prospective Single-Center Phase II Study

“…No differences were seen in the median number of Tregs per μL or in the median frequency of Tregs as percent of CD4 + cells between the groups after mobilization at day 8, either 15 (13)(14)(15)(16)(17)(18)(19) 14 (13)(14)(15)(16) .34 Time to neutrophil engraftment, days 10 (9-11) 10 (9-11) .93 Time to platelet engraftment, days…”

“…Immune suppressive Tregs are found in the microenvironment of malignant tumors, including multiple myeloma, which are associated with poor prognosis [12,13]. New data suggest that enhanced use of G-CSF may induce the generation of Tregs in a dose-dependent manner, which may have a deleterious effect on the immunologic response against tumor cells after ASCT [14,15]. Conversely, other studies report on reduced Treg levels in the leukapheresis products compared with the bone marrow after G-CSF stimulation [16,17].…”