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

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

Research output: Contribution to journalArticle

418 Scopus citations

Abstract

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 monocytederived 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.

Original languageEnglish (US)
Pages (from-to)1167-1181
Number of pages15
JournalJournal of Experimental Medicine
Volume209
Issue number6
DOIs
StatePublished - Jun 4 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Hoeffel, G., Wang, Y., Greter, M., See, P., Teo, P., Malleret, B., Leboeuf, M., Low, D., Oller, G., Almeida, F., Choy, S. H. Y., Grisotto, M., Renia, L., Conway, S. J., Stanley, E. R., Chan, J. K. Y., Ng, L. G., Samokhvalov, I. M., Merad, M., & Ginhoux, F. (2012). Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. Journal of Experimental Medicine, 209(6), 1167-1181. https://doi.org/10.1084/jem.20120340