Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks
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
WEHI Research Division(s)
Molecular Immunology
Rights Notice
Copyright © 2014 by The Rockefeller University Press


Creation Date: 2014-02-18 03:39:52
Last Modified: 0001-01-01 12:00:00
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