Searching for macrophage targets to treat major human diseases

Macrophages are a key tissue cellular compartment where they constantly sense and respond to threats by both shaping the immune response to each specific threat and in helping clear damaged cells. Thus, playing a key role in the maintenance of organismal homeostasis and in clearing injuries.

It is now established that macrophages accumulate in all human lesions and contribute significantly to the outcome of most human diseases.

Our laboratory is mostly interested in the role of macrophages in Cancer and Inflammatory diseases. More than a decade ago, we discovered that macrophages arise from two distinct lineages. The tissue resident macrophage (Trm) lineage and the monocyte-derived macrophage lineage. Trm populate organs in the steady state where they play a key role in organ homeostasis including clearing damaged cells, promoting vascular and neuronal integrity and contributing to maintaining energy expenditure. Trm self-renew locally independent of circulating monocytes and are heavily imprinted by tissue cues. In inflamed states, circulating monocytes are recruited in mass in tissues, where they differentiate into macrophages that share some phenotypic markers with Trm but are fundamentally different in their response to injuries. A big focus of the lab to is to understand the functional specialization and contribution of each macrophage lineage to disease outcome and identify novel macrophage targets of disease.

Key references:

1. Ginhoux et al. Science 2010
2. Muller et al. Cell 2014
3. Hashimoto et al. Immunity 2013
4. Chow et al. Nature Medicine 2013
5. Casanova-acebes et al. Nature 2021