Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes

Immediate precursors of the many subtypes of dendritic cells (DCs) remain obscure. Here we purified a splenic precursor population that produced all splenic CD8(+) and CD8(-) conventional DCs (cDCs) but not plasmacytoid DCs or other lineages. This 'pre-cDC' population included cells 'precommitted' to form either CD8(+) or CD8(-) cDCs. The pre-cDCs, which comprised 0.05% of splenocytes, expressed a CD11c(int)CD45RA(Io)CD43(int)SIRP-alpha(int)CD4(-)CD8(-) major histocompatibility complex class II-negative surface phenotype. The pre-cDCs were not monocytes. Monocytes generated few cDCs in steady-state recipient mice. However, when transferred into mice with an inflammatory milieu dependent on granulocyte-macrophage colony-stimulating factor, monocytes produced a distinct type of splenic DC. Thus, the inflammatory status of the host influences the developmental origin and type of DC present in lymphoid tissues.