Monocyte differentiation within tissues: a renewed outlook

When recruited to mammalian tissues, monocytes differentiate into macrophages or dendritic cells (DCs). In the past few years, the existence of monocyte-derived DCs (moDCs) was questioned by the discovery of new DC populations with overlapping phenotypes. Here, we critically review the evidence for monocyte differentiation into DCs in tissues and highlight their specific functions. Recent studies have shown that monocyte-derived macrophages (moMacs) with distinct life cycles coexist in tissues, both at steady state and upon inflammation. Integrating studies in mice and humans, we highlight specific features of moMacs during inflammation and tissue repair. We also discuss the notion of monocyte differentiation occurring via a binary fate decision. Deciphering monocyte-derived cell properties is essential for understanding their role in nonresolving inflammation and how they might be targeted for therapies.