Colony-stimulating factor (CSF) 1 receptor blockade reduces inflammation in human and murine models of rheumatoid arthritis

CSF-1 or IL-34 stimulation of CSF1R promotes macrophage differentiation, activation and osteoclastogenesis, and pharmacological inhibition of CSF1R is beneficial in animal models of arthritis. The objective of this study was to determine the relative contributions of CSF-1 and IL-34 signaling to CSF...

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Published in:	Arthritis research & therapy 2016-03, Vol.18 (73), p.75-75, Article 75
Main Authors:	Garcia, Samuel, Hartkamp, Linda M, Malvar-Fernandez, B, van Es, Inge E, Lin, Haishan, Wong, Justin, Long, Li, Zanghi, James A, Rankin, Andrew L, Masteller, Emma L, Wong, Brian R, Radstake, Timothy R D J, Tak, Paul P, Reedquist, Kris A
Format:	Article
Language:	eng
Subjects:	Animals Arthritis, Experimental - immunology Arthritis, Experimental - metabolism Arthritis, Experimental - pathology Arthritis, Rheumatoid - immunology Arthritis, Rheumatoid - metabolism Arthritis, Rheumatoid - pathology Benz(a)Anthracenes Complications and side effects Female Flow Cytometry Humans Image Processing, Computer-Assisted Immunohistochemistry Inflammation Inflammation - immunology Inflammation - metabolism Inflammation - pathology Influence Interleukins - biosynthesis Macrophage colony stimulating factor Macrophage Colony-Stimulating Factor - antagonists & inhibitors Macrophage Colony-Stimulating Factor - immunology Macrophages - immunology Macrophages - metabolism Male Mice Mice, SCID Real-Time Polymerase Chain Reaction Receptor, Macrophage Colony-Stimulating Factor - immunology Receptor, Macrophage Colony-Stimulating Factor - metabolism Rheumatoid arthritis Risk factors
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Summary:	CSF-1 or IL-34 stimulation of CSF1R promotes macrophage differentiation, activation and osteoclastogenesis, and pharmacological inhibition of CSF1R is beneficial in animal models of arthritis. The objective of this study was to determine the relative contributions of CSF-1 and IL-34 signaling to CSF1R in RA. CSF-1 and IL-34 were detected by immunohistochemical and digital image analysis in synovial tissue from 15 biological-naïve rheumatoid arthritis (RA) , 15 psoriatic arthritis (PsA) and 7 osteoarthritis (OA) patients . Gene expression in CSF-1- and IL-34-differentiated human macrophages was assessed by FACS analysis and quantitative PCR. RA synovial explants were incubated with CSF-1, IL-34, control antibody (Ab), or neutralizing/blocking Abs targeting CSF-1, IL-34, or CSF1R. The effect of a CSF1R-blocking Ab was examined in murine collagen-induced arthritis (CIA). CSF-1 (also known as M-CSF) and IL-34 expression was similar in RA and PsA synovial tissue, but lower in controls (P
ISSN:	1478-6362 1478-6354 1478-6362