G-CSF and neutrophils are nonredundant mediators of murine experimental autoimmune uveoretinitis
- Author(s)
- Goldberg, GL; Cornish, AL; Murphy, J; Pang, ES; Lim, LL; Campbell, IK; Scalzo-Inguanti, K; Chen, X; McMenamin, PG; Maraskovsky, E; McKenzie, BS; Wicks, IP;
- Details
- Publication Year 2016-01,Volume 186,Issue #1,Page 172-84
- Journal Title
- Am J Pathol
- Publication Type
- Journal Article
- 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.
- Publisher
- Elsevier
- Research Division(s)
- Inflammation
- PubMed ID
- 26718978
- Publisher's Version
- https://doi.org/10.1016/j.ajpath.2015.09.008
- NHMRC Grants
- NHMRC/1034598, NHMRC/1023407, NHMRC/1016647,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-01-29 11:46:02
Last Modified: 2016-01-29 12:28:00