G-CSF and neutrophils are nonredundant mediators of murine experimental autoimmune uveoretinitis
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
WEHI Research Division(s)
Inflammation
PubMed ID
26718978
NHMRC Grants
NHMRC/1034598 NHMRC/1023407 NHMRC/1016647
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
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