Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophages

• DOI: 10.1084/jem.20120340
• Publication Date: 2012-05-08T06:55:26Z
• Authors: Guillaume Hoeffel; Yilin Wang; Melanie Greter; Peter See; Pearline Teo; Benoit Malleret; Marylène Leboeuf; Donovan Low; Guillaume Oller; Francisca Almeida; Sharon H.Y. Choy; Marcos Grisotto; Laurent Renia; Simon J. Conway; E. Richard Stanley; Jerry K.Y. Chan; Lai Guan Ng; Igor M. Samokhvalov; Miriam Merad; Florent Ginhoux
• Keywords: 570; 0303 health sciences; Macrophages; Stem Cells; Age Factors; 610; Article; Monocytes; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Liver; Pregnancy; Langerhans Cells; Animals; Cell Lineage; Female; Microglia; Myeloid Progenitor Cells; Skin; Yolk Sac

Langerhans cells (LCs) are the dendritic cells (DCs) of the epidermis, forming one of the first hematopoietic lines of defense against skin pathogens. In contrast to other DCs, LCs arise from hematopoietic precursors that seed the skin before birth. However, the origin of these embryonic precursors remains unclear. Using in vivo lineage tracing, we identify a first wave of yolk sac (YS)–derived primitive myeloid progenitors that seed the skin before the onset of fetal liver hematopoiesis. YS progenitors migrate to the embryo proper, including the prospective skin, where they give rise to LC precursors, and the brain rudiment, where they give rise to microglial cells. However, in contrast to microglia, which remain of YS origin throughout life, YS-derived LC precursors are largely replaced by fetal liver monocytes during late embryogenesis. Consequently, adult LCs derive predominantly from fetal liver monocyte-derived cells with a minor contribution of YS-derived cells. Altogether, we establish that adult LCs have a dual origin, bridging early embryonic and late fetal myeloid development.