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

Abstract

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.