title: G-CSF treatment promotes apoptosis of autoreactive T cells to restrict the inflammatory cascade and accelerate recovery in experimental allergic encephalomyelitis.
abstract: G-CSF is a hematopoietic growth factor that regulates the proliferation, differentiation and survival of myeloid lineage cells, which has protective effects in autoimmune neuroinflammatory diseases such as EAE. Here we use EAE model treated by G-CSF to address the hypothesis that G-CSF inhibits the proliferative response of splenic T cells via the enhancement of apoptosis, and this priming effect of G-CSF depends on the cell cycle. Our results show that G-CSF administration reduced EAE frequency and severity of attacks. The inflammatory cells and demyelination areas were decreased in the CNS of G-CSF-treated mice. G-CSF treatment altered cytokine profiles in vivo to inhibit the productions of IFN-γ, IL-1β, IL-2, TNF-α, IL-17 and NO, while the secretions of IL-4 and IL-10 were increased. Splenic T cells from G-CSF-treated mice showed significantly lower proliferative response to specific antigen MOG35-55stimulation. G-CSF enhanced the percentage of a CD4+CD25+T cell subset in spleen T cells. Moreover, G-CSF promoted the G0/G1 to S phase transition of MOG35-55autoreactive T cells inducing apoptosis and elevating Bax gene expression of apoptosis marker. These findings indicate that G-CSF treatment induces the apoptosis of MOG35-55autoreactive T cells, which decreases the production of pro-inflammatory cytokines and NO, suppresses the proliferation of autoreactive T cells and elevates a CD4+CD25+T cell subset to inhibit inflammatory infiltration and demyelination within CNS of EAE. The conclusions of G-CSF treatment in EAE mice suggest that G-CSF is clinically applicable and may be considered for future use in therapeutic measures for multiple sclerosis treatment.
authors: Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan 637000, P. R. China; Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Sderot Churchill, Jerusalem, 91240, Israel. Electronic address: pengwei39@hotmail.com.
authors: Wei
authors: W
authors: Peng
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity; D037342:Pertussis Toxin / Q000633:toxicity; D020127:Recovery of Function / Q000187:drug effects*; D013154:Spleen / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D017304:Annexin A5; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D051028:bcl-2-Associated X Protein; C445081:myelin oligodendrocyte glycoprotein (35-55); D016179:Granulocyte Colony-Stimulating Factor; D009569:Nitric Oxide; D005620:Freund's Adjuvant; D037342:Pertussis Toxin
keywords: Apoptosis; Autoreactive T cells; Experimental allergic encephalomyelitis; Granulocyte colony-stimulating factor