Reprogramming of macrophages — new opportunities for therapeutic targeting

•Macrophage activation is best described by a multi-dimensional model.•Targeting macrophages specifically requires a multi-modal approach.•Macrophage reprogramming rather than deletion might be a future therapeutic avenue.•Transcriptional and epigenetic control might be new drug targets in macrophages.

Macrophages are key players of tissue homeostasis and are cells involved in all major human diseases including infections, tumors, western life-style associated diseases and even neurodegenerative diseases. Therefore, specifically targeting macrophages seems to be an attractive therapeutic approach, yet such strategies have not been successfully translated to the clinic. An important hallmark of macrophages is their astounding plasticity and their capacity to integrate microenvironmental signals to perform distinct biological functions. Understanding the cellular programming of macrophages during such events will be a fundamental pre-requisite to develop targeted therapeutic approaches in human diseases. Here, I highlight recent findings of how macrophage activation is regulated and how one can envision much more specific approaches of targeting macrophages.