G-CSF and neutrophils are nonredundant mediators of murine experimental autoimmune uveoretinitis

Gabrielle L. Goldberg, Ann L. Cornish, Jane Murphy, Ee Shan Pang, Lyndell L. Lim, Ian K. Campbell, Karen Scalzo-Inguanti, Xiangting Chen, Paul G. McMenamin, Eugene Maraskovsky, Brent S. McKenzie, Ian P. Wicks

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20 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)172-184
Number of pages13
JournalAmerican Journal of Pathology
Issue number1
Publication statusPublished - Jan 2016

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