Francqui Collen Start-Up Grant 2021 Kiavash Movahedi

Macrophages are found in all organs and play an instrumental role in regulating tissue homeostasis
and inflammatory responses. Since their discovery more than a century ago, we have witnessed
several conceptual advances that have dramatically changed our view of these cells. The initial dogma
regarded macrophages merely as dormant immune sentinels or as “garbage disposal units”. This
assumption has been completely overthrown. Transcriptomic profiling of macrophages has
demonstrated their astonishing tissue diversity1
. We now know that macrophages are highly adapted
to their tissue of residence and perform unique local functions2
. The brain forms no exception, and
it is now well established that microglia - the resident macrophages of the brain parenchyma - are
critical for maintaining healthy brain physiology3
. The brain also contains other tissue-resident
macrophages, which are found at its border regions (perivascular space, meninges and choroid
plexus)4
, which are strategically important sites that act as an entry gate for immune cells. Genomewide association studies have convincingly predicted the involvement of microglia/macrophages in
many neurodegenerative disorders, including Alzheimer's disease5
. However, their role in these
disorders remains highly elusive. Macrophages are also critical components of the tumor
microenvironment and are thought to be involved in all facets of tumor progression6
. Most solid
tumors show a high infiltration of Tumor-Associated Macrophages and these cells form an attractive
therapeutic target. However, developing successful macrophage-centered therapies for cancer or
other brain disorders remains a major challenge.