Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks
- Author(s)
- Chopin, M; Seillet, C; Chevrier, S; Wu, L; Wang, H; Morse, HC, 3rd; Belz, GT; Nutt, SL;
- Details
- Publication Year 2013-12-16,Volume 210,Issue #13,Page 2967-80
- Journal Title
- The Journal of experimental medicine
- Publication Type
- Journal Article
- Abstract
- Langerhans cells (LCs) are the unique dendritic cells found in the epidermis. While a great deal of attention has focused on defining the developmental origins of LCs, reports addressing the transcriptional network ruling their differentiation remain sparse. We addressed the function of a group of key DC transcription factors-PU.1, ID2, IRF4, and IRF8-in the establishment of the LC network. We show that although steady-state LC homeostasis depends on PU.1 and ID2, the latter is dispensable for bone marrow-derived LCs. PU.1 controls LC differentiation by regulating the expression of the critical TGF-beta responsive transcription factor RUNX3. PU.1 directly binds to the Runx3 regulatory elements in a TGF-beta-dependent manner, whereas ectopic expression of RUNX3 rescued LC differentiation in the absence of PU.1 and promoted LC differentiation from PU.1-sufficient progenitors. These findings highlight the dual molecular network underlying LC differentiation, and show the central role of PU.1 in these processes.
- Publisher
- Rockefeller University Press
- Research Division(s)
- Molecular Immunology
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865480/
- Publisher's Version
- https://doi.org/10.1084/jem.20130930
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Creation Date: 2014-02-18 03:39:52