New Therapeutic Avenues of mCSF for Brain Diseases and Injuries.

Serge Rivest,Vincent Pons

doi:10.3389/fncel.2018.00499

Abstract

Macrophage colony-stimulating factor (mCSF) is a cytokine known to promote the recruitment of macrophages inducing the release of CCL2, a chemokine mobilizing monocytes to sites of inflammation. Additionally, it induces microglia/macrophage proliferation and the polarization of these cells towards a M2-like phenotype, impairing their ability to release pro-inflammatory factors and toxic mediators, while favoring the release of mediators promoting tissue repair. Another important player is the mCSF receptor CSFR1, which is highly expressed in monocytes, macrophages and microglia. Here, we discuss the new interesting therapeutic avenue of the mCSF/CSFR1 axis on brain diseases. More specifically, mCSF cascade might stimulate the survival/proliferation of oligodendrocytes, enhance the immune response as well as modulate the release of growth factors and the phagocytic activity of immune cells to remove myelin debris and toxic proteins from the brain.

Highlights

Macrophage colony-stimulating factor is an hematopoietic cytokine expressed in a wide range of cells and tissues, namely the kidney, brain, liver, retina, spleen, lung, adipose tissue, skin and joints (Ryan, 2001; Nandi, 2006)
It stimulates progenitor cells from bone marrow (Stanley, 1976) and takes a role in the development, proliferation and maintenance of mononuclear phagocytes such as monocytes, dendritic cells, microglia and osteoclasts (Chitu et al, 2016). Macrophage colony-stimulating factor (mCSF) signals through a tyrosine kinase family receptor, CSFR1 known as CD115, which binds interleukin-34 (IL-34) that plays similar roles (Ségaliny et al, 2015)
CSFR1 monoclonal antibody or antagonist has been shown to suppress the inflammatory response in a phase II clinical trial on rheumatoid arthritis (Garcia et al, 2013). mCSF-deficient mice exhibit numerous phenotypic defects, namely toothless, skeletal defects (Naito et al, 1997), reduced body weight, deficit in tissue macrophages and osteoclasts as well as neurological abnormalities (Nandi et al, 2012) indicating a major role played by this ligand on these populations of cells

Summary

Vincent Pons and Serge Rivest *

Helena Brigas, Universidade de Lisboa, Portugal, in collaboration with reviewer LL. Macrophage colony-stimulating factor (mCSF) is a cytokine known to promote the recruitment of macrophages inducing the release of CCL2, a chemokine mobilizing monocytes to sites of inflammation It induces microglia/macrophage proliferation and the polarization of these cells towards a M2-like phenotype, impairing their ability to release pro-inflammatory factors and toxic mediators, while favoring the release of mediators promoting tissue repair. Another important player is the mCSF receptor CSFR1, which is highly expressed in monocytes, macrophages and microglia. MCSF cascade might stimulate the survival/proliferation of oligodendrocytes, enhance the immune response as well as modulate the release of growth factors and the phagocytic activity of immune cells to remove myelin debris and toxic proteins from the brain

INTRODUCTION

BRAIN INJURY

CONCLUSION