Rebecca Gentek, Clément Ghigo, Guillaume Hoeffel, Audrey Jorquera, Rasha Msallam, Stephan Wienert, Frederick Klauschen, Florent Ginhoux, Marc Bajénoff; Epidermal γδ T cells originate from yolk sac hematopoiesis and clonally self-renew in the adult. J Exp Med 3 December 2018; 215 (12): 2994–3005. doi: https://doi.org/10.1084/jem.20181206
The murine epidermis harbors two immune cell lineages, Langerhans cells (LCs) and γδ T cells known as dendritic epidermal T cells (DETCs). LCs develop from both early yolk sac (YS) progenitors and fetal liver monocytes before locally self-renewing in the adult. For DETCs, the mechanisms of homeostatic maintenance and their hematopoietic origin are largely unknown. Here, we exploited multicolor fate mapping systems to reveal that DETCs slowly turn over at steady state. Like for LCs, homeostatic maintenance of DETCs is achieved by clonal expansion of tissue-resident cells assembled in proliferative units. The same mechanism, albeit accelerated, facilitates DETC replenishment upon injury. Hematopoietic lineage tracing uncovered that DETCs are established independently of definitive hematopoietic stem cells and instead originate from YS hematopoiesis, again reminiscent of LCs. DETCs thus resemble LCs concerning their maintenance, replenishment mechanisms, and hematopoietic development, suggesting that the epidermal microenvironment exerts a lineage-independent influence on the initial seeding and homeostatic maintenance of its resident immune cells.
This study was funded by grants from the Agence National pour la Recherche (ANR-10-INBS-04-01 France-BioImaging, ANR-08-JCJC-0134). Additional support was provided by institutional grants from Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, and Aix-Marseille University to the Centre d'Immunologie de Marseille-Luminy. F. Ginhoux is a European Molecular Biology
Organization Young Investigators Programme awardee and is supported by Singapore Immunology Network core funding as well as a Singapore National Research Foundation Senior Investigatorship (NRF2016NRF-NRFI001-02).