CSF-1 receptor signaling and blockade strategies. CSF-1 and IL-34 bind to the extracellular domain of the CSF-1R to induce dimerization and tyrosine kinase (TK)–mediated autophosphorylation of cytoplasmic tyrosine residues, leading to a cascade of intracellular signals, which regulate the production, survival, and function of macrophages. To date, no alternative receptor for IL-34 has been identified. Disruption of the CSF-1/CSF-1R axis can be achieved using neutralizing anti–CSF-1 mAbs or anti–CSF-1R mAbs (the latter can block binding of either CSF-1 or IL-34 or both cytokines) or inhibition of CSF-1R tyrosine kinase using small-molecule TK inhibitors.