title: G-CSF and Neutrophils Are Nonredundant Mediators of Murine Experimental Autoimmune Uveoretinitis.
abstract: Granulocyte colony-stimulating factor (G-CSF) is a regulator of neutrophil production, function, and survival. Herein, we investigated the role of G-CSF in a murine model of human uveitis-experimental autoimmune uveoretinitis. Experimental autoimmune uveoretinitis was dramatically reduced in G-CSF-deficient mice and in anti-G-CSF monoclonal antibody-treated, wild-type (WT) mice. Flow cytometric analysis of the ocular infiltrate in WT mice with experimental autoimmune uveoretinitis showed a mixed population, comprising neutrophils, macrophages, and T cells. The eyes of G-CSF-deficient and anti-G-CSF monoclonal antibody-treated WT mice had minimal neutrophil infiltrate, but no change in other myeloid-derived inflammatory cells. Antigen-specific T-cell responses were maintained, but the differentiation of pathogenic type 17 helper T cells in experimental autoimmune uveoretinitis was reduced with G-CSF deficiency. We show that G-CSF controls the ocular neutrophil infiltrate by modulating the expression of C-X-C chemokine receptors 2 and 4 on peripheral blood neutrophils, as well as actin polymerization and migration. These data reveal an integral role for G-CSF-driven neutrophil responses in ocular autoimmunity, operating within and outside of the bone marrow, and also identify G-CSF as a potential therapeutic target in the treatment of human uveoretinitis.
authors.affiliation: Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Gabrielle L
authors.initials: GL
authors.lastname: Goldberg
authors.affiliation: Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ann L
authors.initials: AL
authors.lastname: Cornish
authors.affiliation: Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Murphy
authors.affiliation: Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ee Shan
authors.initials: ES
authors.lastname: Pang
authors.affiliation: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
authors.forename: Lyndell L
authors.initials: LL
authors.lastname: Lim
authors.affiliation: CSL Limited, Bio21 Institute, Parkville, Victoria, Australia.
authors.forename: Ian K
authors.initials: IK
authors.lastname: Campbell
authors.affiliation: CSL Limited, Bio21 Institute, Parkville, Victoria, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Scalzo-Inguanti
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Xiangting
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Paul G
authors.initials: PG
authors.lastname: McMenamin
authors.affiliation: CSL Limited, Bio21 Institute, Parkville, Victoria, Australia.
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.affiliation: CSL Limited, Bio21 Institute, Parkville, Victoria, Australia.
authors.forename: Brent S
authors.initials: BS
authors.lastname: McKenzie
authors.affiliation: Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia; Department of Rheumatology, Royal Melbourne Hospital, Parkville, Victoria, Australia; Department of Medicine, University of Melbourne, Parkville, Victoria, Australia. Electronic address: wicks@wehi.edu.au.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Wicks
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D014605:Uveitis / Q000276:immunology* / Q000473:pathology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor