Csf1r, the Colony-Stimulating Factor-1 Receptor, is a receptor tyrosine kinase. It is crucial for the differentiation and maintenance of most tissue-resident macrophages and bone-resorbing osteoclasts. Activation by cytokine ligation to its ectodomain triggers autophosphorylation of the intracellular tyrosine kinase domain, activating downstream pro-survival kinase cascades like PI3K, ERK1/2, and JNK [1].

In mice, deletion of the fms-intronic regulatory element (FIRE), a super-enhancer in the Csf1r locus, selectively impacts Csf1r expression and tissue macrophage development. Csf1rΔFIRE/ΔFIRE mice lack macrophages in the embryo, brain microglia, and resident macrophages in several tissues, while other macrophage populations and monocytes' homeostasis remain unaffected, except monocytes and their progenitors in bone marrow lacking surface Csf1r [3]. Also, in a mouse model of graft-versus-host disease, CSF1R inhibition led to exacerbated neuroinflammation and behavioral deficits [4].

In conclusion, Csf1r is essential for the development and function of specific macrophage populations. Mouse models with targeted Csf1r modifications, such as the Csf1rΔFIRE/ΔFIRE mice, have revealed its tissue-specific roles. These models also show that Csf1r has implications in diseases like leukoencephalopathy, cancer, and graft-versus-host disease, highlighting its potential as a therapeutic target in these areas [2,1,4].