Abstract
The suppressor of cytokine signalling protein 3 (SOCS3) critically controls immune cell activation, although its role in macrophage polarization and function remains controversial. Using experimental autoimmune uveoretinitis (EAU) as a model, we show that inflammation-mediated retinal degeneration is exaggerated and retinal angiogenesis is accelerated in mice with SOCS3 deficiency in myeloid cells (LysMCre/+SOCS3fl/fl). At the acute stage of EAU, the population of infiltrating neutrophils was increased and the population of macrophages decreased in LysMCre/+SOCS3fl/flmice compared to that in WT mice. Real-time reverse transcription-PCR showed that the expression of tumor necrosis factor-α, IL-1β, interferon-γ, granulocyte-macrophage colony-stimulating factor, and Arginase-1 was significantly higher in the LysMCre/+SOCS3fl/flEAU retina in contrast to WT EAU retina. The percentage of Arginase-1+infiltrating cells was significantly higher in the LysMCre/+SOCS3fl/flEAU retina than that in the WT EAU retina. In addition, bone-marrow-derived macrophages and neutrophils from the LysMCre/+SOCS3fl/flmice express significantly higher levels of CCL2 and Arginase-1 compared to those from WT mice. Inhibition of Arginase using an L-arginine analog amino-2-borono-6-hexanoic suppressed inflammation-induced retinal angiogenesis without affecting the severity of inflammation. Our results suggest that SOCS3 critically controls the phenotype and function of macrophages and neutrophils under inflammatory conditions and loss of SOCS3 promotes the angiogenic phenotype of the cells through up-regulation of Arginase-1.
Original language | English |
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Pages (from-to) | 1007-1020 |
Number of pages | 14 |
Journal | The American Journal of Pathology |
Volume | 188 |
Issue number | 4 |
Early online date | 13 Feb 2018 |
DOIs | |
Publication status | Published - Apr 2018 |
Bibliographical note
Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.Keywords
- Journal Article
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Dive into the research topics of 'Cytokine Signaling Protein 3 (SOCS3) deficiency in myeloid cells promotes retinal degeneration and angiogenesis through arginase-1 up-regulation in experimental autoimmune uveoretinitis'. Together they form a unique fingerprint.Student theses
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