The multifaceted effects of granulocyte colony-stimulating factor in immunomodulation and potential roles in intestinal immune homeostasis

Abstract

The three colony-stimulating factors, granulocyte/macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and granulocyte colony-stimulating factor (G-CSF), have been regarded as immunostimulators because of their role in granulocyte and myeloid hematopoiesis and immune function. However, unlike GM-CSF and M-CSF, G-CSF possesses immunosuppressive effects on other immune cells including monocytes/macrophages, dendritic cells, and T lymphocytes when exogenously administered. Given the immunomodulatory effects of exogenous G-CSF, endogenous G-CSF may also play an important role in maintaining local immune homeostasis in tissue in which it is highly and constitutively produced. This review highlights the potential role of G-CSF in immunomodulation and intestinal immune homeostasis.

Figure 1

Model of the role of G-CSF in the intestine. G-CSF may exert immunomodulatory effects in the intestine through multiple mechanisms. Intestinal G-CSF may be produced by macrophages or subepithelial myofibroblasts, induced or modulated by luminal bacteria or endogenous factors such as serum amyloid A (SAA). G-CSF can then act locally to strengthen the barrier protecting epithelial cells from injury-induced apoptosis and stimulating neutrophil effector function to aid in the clearance of translocated bacteria. At the same time, G-CSF may have immunoregulatory effects on macrophages, dendritic cells, as well as Th1 and Th17 responses.