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 leads to autophosphorylation of its intracellular tyrosine kinase domain, triggering downstream pro-survival kinase cascades like PI3K, ERK1/2, and JNK [1].

In mice, deletion of the Csf1r enhancer (FIRE) 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 the homeostasis of other macrophage populations and monocytes remains unaffected, except monocytes and their progenitors in bone marrow lack surface Csf1r. These mice are healthy and fertile, providing a model to study tissue-specific macrophage functions [2]. In a cGVHD mouse model, CSF1R inhibition promoted neuroinflammation and behavioral deficits, suggesting unexpected neurological immune toxicity during CSF1R blockade [3].

In conclusion, Csf1r is essential for the development and function of specific macrophage populations. Gene-modified mouse models, such as Csf1rΔFIRE/ΔFIRE mice, have revealed its tissue-specific roles in macrophage development. Additionally, the study of Csf1r in disease models like cGVHD has provided insights into potential adverse effects of its inhibition, contributing to our understanding of its functions in disease conditions.