Article

Colony-stimulating factor in inflammation and autoimmunity

Arthritis and Inflammation Research Centre and Cooperative Research Centre for Chronic Inflammatory Diseases, University of Melbourne, Department of Medicine, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Nature Reviews Immunology (Impact Factor: 34.99). 08/2008; 8(7):533-44. DOI: 10.1038/nri2356
Source: PubMed

ABSTRACT

Although they were originally defined as haematopoietic-cell growth factors, colony-stimulating factors (CSFs) have been shown to have additional functions by acting directly on mature myeloid cells. Recent data from animal models indicate that the depletion of CSFs has therapeutic benefit in many inflammatory and/or autoimmune conditions and as a result, early-phase clinical trials targeting granulocyte/macrophage colony-stimulating factor and macrophage colony-stimulating factor have now commenced. The distinct biological features of CSFs offer opportunities for specific targeting, but with some associated risks. Here, I describe these biological features, discuss the probable specific outcomes of targeting CSFs in vivo and highlight outstanding questions that need to be addressed.

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    • "CSF1R expression has been reported on immunosuppressive myeloid cells and dendritic cells [41] [42] [43]. CSF1-CSF1R signaling regulates survival, differentiation, and proliferation of monocytes and macrophages [44] [45], and have critical role in angiogenesis and tumor progression [46] [47]. Therefore, the goals of the present study are to (1) investigate the effect of CSF1R blockade on orthotopic glioma development in a recently established preclinical chimeric mouse model, (2) to evaluate whether CSF1R blockade alone or in combination with VEGFR2 blockade could inhibit the homing of myeloid BMDCs to the glioma, (3) to identify signature immune cell populations following CSF1R inhibition that could have profound role in glioma growth and (4) to investigate key secreted molecular signatures in GBM TME following CSF1R inhibition. "
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    • "Caescu et al. [50] showed that treatment of macrophages with CSF1 upregulates miR-21 resulting in a robust anti-inflammatory effect which favors M2 differentiation [50]. This is in agreement with the concept of CSF1 receptor signaling being essential for M2 differentiation and inhibition of the M1 phenotype [51]. Wang et al. [52] found that in thioglycollate-elicited peritoneal macrophages miR-21 is downregulated by activation of a prostaglandin E 2 (PGE 2 )/cyclic AMP pathway which results in enhanced expression of M2-but not M1-related genes. "
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