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

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)172-184
Number of pages13
JournalAmerican Journal of Pathology
Volume186
Issue number1
DOIs
Publication statusPublished - Jan 2016

Cite this

Goldberg, G. L., Cornish, A. L., Murphy, J., Pang, E. S., Lim, L. L., Campbell, I. K., ... Wicks, I. P. (2016). G-CSF and neutrophils are nonredundant mediators of murine experimental autoimmune uveoretinitis. American Journal of Pathology, 186(1), 172-184. https://doi.org/10.1016/j.ajpath.2015.09.008
Goldberg, Gabrielle L. ; Cornish, Ann L. ; Murphy, Jane ; Pang, Ee Shan ; Lim, Lyndell L. ; Campbell, Ian K. ; Scalzo-Inguanti, Karen ; Chen, Xiangting ; McMenamin, Paul G. ; Maraskovsky, Eugene ; McKenzie, Brent S. ; Wicks, Ian P. / G-CSF and neutrophils are nonredundant mediators of murine experimental autoimmune uveoretinitis. In: American Journal of Pathology. 2016 ; Vol. 186, No. 1. pp. 172-184.
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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.",
author = "Goldberg, {Gabrielle L.} and Cornish, {Ann L.} and Jane Murphy and Pang, {Ee Shan} and Lim, {Lyndell L.} and Campbell, {Ian K.} and Karen Scalzo-Inguanti and Xiangting Chen and McMenamin, {Paul G.} and Eugene Maraskovsky and McKenzie, {Brent S.} and Wicks, {Ian P.}",
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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 2016, 'G-CSF and neutrophils are nonredundant mediators of murine experimental autoimmune uveoretinitis' American Journal of Pathology, vol. 186, no. 1, pp. 172-184. https://doi.org/10.1016/j.ajpath.2015.09.008

G-CSF and neutrophils are nonredundant mediators of murine experimental autoimmune uveoretinitis. / Goldberg, Gabrielle L.; Cornish, Ann L.; Murphy, Jane; Pang, Ee Shan; Lim, Lyndell L.; Campbell, Ian K.; Scalzo-Inguanti, Karen; Chen, Xiangting; McMenamin, Paul G.; Maraskovsky, Eugene; McKenzie, Brent S.; Wicks, Ian P.

In: American Journal of Pathology, Vol. 186, No. 1, 01.2016, p. 172-184.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - G-CSF and neutrophils are nonredundant mediators of murine experimental autoimmune uveoretinitis

AU - Goldberg, Gabrielle L.

AU - Cornish, Ann L.

AU - Murphy, Jane

AU - Pang, Ee Shan

AU - Lim, Lyndell L.

AU - Campbell, Ian K.

AU - Scalzo-Inguanti, Karen

AU - Chen, Xiangting

AU - McMenamin, Paul G.

AU - Maraskovsky, Eugene

AU - McKenzie, Brent S.

AU - Wicks, Ian P.

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N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pubmed/26718978

U2 - 10.1016/j.ajpath.2015.09.008

DO - 10.1016/j.ajpath.2015.09.008

M3 - Article

VL - 186

SP - 172

EP - 184

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

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