Coordinated expression of tyro3, axl, and mer receptors in macrophage ontogeny

The TAM receptors (Tyro3, Axl, and Mer) are a family of homologous receptor-tyrosine kinases that inhibit Toll-like receptor signaling to regulate downstream pathways and restore homeostasis. TAM triple mutant mice (Tyro3(−/−), Axl(−/−), Mer(−/−)) have elevated levels of pro-inflammatory cytokines and are prone to developing lymphoproliferative disorders and autoimmunity. Understanding differential expression of TAM receptors among human subjects is critical to harnessing this pathway for therapeutic interventions. We have quantified changes in TAM expression during the ontogeny of human macrophages using paired samples of monocytes and macrophages to take advantage of characteristic expression within an individual. No significant differences in levels of Tyro3 were found between monocytes and macrophages (flow cytometry: p=0.652, immunoblot: p=0.231, qPCR: p=0.389). Protein levels of Axl were reduced (flow cytometry: p=0.049, immunoblot: p<0.001) when monocytes matured to macrophages. No significant differences in the levels of Axl mRNA transcripts were found (qPCR: p=0.082), however, Tyro3 and Axl were proportionate. The most striking difference was upregulation of expression of Mer with both protein and mRNA being significantly increased when monocytes developed into macrophages (flow cytometry: p<0.001, immunoblot: p<0.001, qPCR: p=0.004). A fuller characterization of TAM receptor expression in macrophage ontogeny informs our understanding of their function and potential therapeutic interventions.