Figure 2. Macrophage Lineages Re-Defined in Mice.

The mononuclear phagocytic system in adults derives from at least three sources. The first is the yolk sac (YS) that results in progenitors that populate all tissues and their progeny persist throughout life as F4/80 bright resident macrophages. These lineages are largely regulated by CSF1R. The second from the fetal liver is less well defined but seems to contribute to adult LCs perhaps through a progenitor derived from the YS. The third lineage derives from the bone marrow (BM) to give circulating monocytes and their progeny F4/80^low macrophages and DCs. In this case the Ly6c+ monocytes give rise to classical DCs under the regulation of FLT3 and these are continuously replenished. Other macrophages that are F4/80 low also emanate from Ly6c⁺ monocytes and in some cases such as kidney and lung, co-exist with those derived from YS to give chimeric organs. The exact role of the patrolling Ly6cmacrophages remains unclear, as is the contribution of fetal liver to adult tissue macrophages.