IL-34 and CSF-1, deciphering similarities and differences at steady state and in diseases

Although IL-34 and CSF-1 share actions as key mediators of monocytes/macrophages survival and differentiation, they also display differences that should be identified to better define their respective roles in health and diseases. IL-34 displays low sequence homology with CSF-1 but has a similar general structure and they both bind to a common receptor CSF-1R, although binding and subsequent intracellular signaling shows differences. CSF-1R expression has been until now mainly described at a steady state in monocytes/macrophages and myeloid dendritic cells, as well as in some cancers. IL-34 has also 2 other receptors, protein-tyrosine phosphatase zeta (PTPζ) and CD138 (Syndecan-1), expressed in some epithelium, cells of the central nervous system (CNS), as well as in numerous cancers. While most, if not all, of CSF-1 actions are mediated through monocyte/macrophages, IL-34 has also other potential actions through PTPζ and CD138. Additionally, IL-34 and CSF-1 are produced by different cells in different tissues. This review describes and discusses similarities and differences between IL-34 and CSF-1 at steady state and in pathological situations and identifies possible ways to target IL-34, CSF-1, and its receptors.