Cytokines 2017

Monocytes give rise to macrophages and dendritic cells (DCs) under steady-state and inflammatory conditions, thereby contributing to host defense and tissue pathology. Inflammation can prompt tissue-infiltrating monocytes to differentiate into monocyte-derived macrophages and DCs, which are associated with both homeostatic host-defense reactions and inflammatory diseases. In mice, monocytes are divided into classical Ly6c^hi and non-classical Ly6c^lo-expressing subsets. Ly6c^lo monocytes are present only in the blood, whereas Ly6c^hi monocytes are found in both the blood and other tissues, where they differentiate into macrophages and DCs. In this context, most Ly6c^lo monocytes are derived from Ly6chi monocytes. In human, monocytes are comprised of major CD14⁺CD16⁻ and other CD14⁺CD16⁺ and CD14^loCD16⁺ monocytes. A couple of years ago, a common monocyte progenitor (cMoP) that is restricted to the monocyte lineage has been identified in mice. Here, we introduce human cMoP, which was identified as a CLEC12A^hiCD64^hi subpopulation of conventional granulocyte-monocyte progenitors (cGMP) in umbilical cord blood and in bone marrow. Human cMoP gave rise to monocyte subsets without showing any potential for differentiating into myeloid or lymphoid cells ex vivo. Within the cGMP population, we also identified revised GMP that completely lacked DC and lymphoid potential, and the revised GMP gave rise sequentially to cMoP, pre-monocytes, and monocytes Collectively, our findings revise the current understanding of human myeloid cell differentiation pathways. Given that monocytes and monocyte-derived macrophages and osteoclast cause a variety of inflammatory disorders, our studies shed light not only on human monocyte differentiation.