title: Granulocyte colony-stimulating factor treatment ameliorates lupus nephritis through the expansion of regulatory T cells.
abstract: Granulocyte 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  G-CSF treatment ameliorated lupus nephritis through the preferential expansion of CD4+CD25+Foxp3+Tregs. Therefore, G-CSF has a therapeutic potential for lupus nephritis.
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Ji-Jing
authors.initials: JJ
authors.lastname: Yan
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Enkthuya
authors.initials: E
authors.lastname: Jambaldorj
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Jae-Ghi
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Shim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Miyeun
authors.initials: M
authors.lastname: Han
authors.affiliation: Transplantation Center, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
authors.forename: Tai Yeon
authors.initials: TY
authors.lastname: Koo
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. jcyjs@dreamwiz.com.|Transplantation Center, Seoul National University Hospital, Seoul, 03080, Republic of Korea. jcyjs@dreamwiz.com.|Department of Surgery, Seoul National University Hospital, Seoul, 03080, Republic of Korea. jcyjs@dreamwiz.com.
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000178:diet therapy* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: Granulocyte colony-stimulating factor; Lupus nephritis; Regulatory T cells