Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks

Michaël Chopin, Cyril Seillet, Stéphane Chevrier, Li Wu, Hongsheng Wang, Herbert C. Morse, Gabrielle T. Belz, Stephen L. Nutt

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91 Citations (Scopus)

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-β responsive transcription factor RUNX3. PU.1 directly binds to the Runx3 regulatory elements in a TGF-β-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.

Original languageEnglish
Pages (from-to)2967-2980
Number of pages14
JournalJournal of Experimental Medicine
Volume210
Issue number13
DOIs
Publication statusPublished - Dec 2013
Externally publishedYes

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