Zeitschrift für klinische und zelluläre Immunologie
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Abstrakt

Colony-Stimulating Factor-1 Receptor in the Polarization of Macrophages: A Target for Turning Bad to Good Ones?

Elisabetta Rovida and Persio Dello Sbarba

Macrophages, which are found in all tissues, are an essential component of the innate immune system, and they play important roles in host defense, inflammation, autoimmune diseases as well as cancer. Functionally, macrophages are classified into two types: classically-activated M1 macrophages and alternatively-activated M2 macrophages. The M1 macrophages typically produce high levels of proinflammatory cytokines and chemokines, whereas M2 macrophages show an efficient phagocytic and scavenging activity. Because the phenotypes of polarized M1 and M2 macrophages can be induced, and reversed to some extent, by various signals, different phases of many diseases are associated with dynamic changes in the balance between M1 and M2 macrophages. The colony-stimulating factor 1 receptor (CSF-1R), a class III receptor tyrosine kinase, sustains the survival, proliferation and differentiation of monocytes and macrophages. Drugging CSF-1R may be the only way to target macrophages within a pathological context. However, CSF-1R-dependent signals may be either positive or detrimental depending on the disease and even on the phase of disease. The role of CSF-1R and its ligands, the colony-stimulating factor-1 and interleukin-34, in macrophages with respect to the pathogenesis of several inflammatory or neoplastic diseases has been reviewed previously. This review will focus specifically on evidences obtained about the role of CSF-1R in macrophage polarization in the context of physiological as well as pathological conditions including inflammation and cancer. The possibility to target CSF-1R, using the several inhibitors already available, for the treatment of inflammatory diseases as well as cancer will be also discussed.